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  • Electronic Resource  (6,221)
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  • 1985-1989
  • 1980-1984  (1,935)
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  • 1
    Electronic Resource
    Electronic Resource
    Enzymatic and pharmacokinetic studies on the metabolism of branched chain α-keto acids in the rat (1983)
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    Details
    ISSN: 1436-6215
    Keywords: branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Description / Table of Contents: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notes: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02020781
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  • 2
    Electronic Resource
    Electronic Resource
    Application of the short-time staining for the electron microscopic investigation of the crystallization of polyethylene (1983)
    Springer
    Colloid & polymer science 261 (1983), S. 373-374 
    Details
    ISSN: 1435-1536
    Keywords: Electron microscopy ; short-time staining ; nodular structure ; crystallization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01413947
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  • 3
    Electronic Resource
    Electronic Resource
    A second look at intraepithelial Langerhans cells in mycosis fungoides and related disorders (1983)
    Springer
    Virchows Archiv 402 (1983), S. 47-60 
    Details
    ISSN: 1432-2307
    Keywords: Mycosis fungoides ; Premycotic lesions ; Parapsoriasis en Plaques ; Langerhans cells ; Virus-like particles ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin biopsies of patients with small and large plaque parapsoriasis, premycotic lesions and mycosis fungoides in different stages were examined. Special attention was paid to the relationships between Langerhans cells (LC) and the neighbouring keratinocytes and lymphocytes. At the contact areas of LC and keratinocytes as well as LC and lymphocytes, particular cell membrane phenomena were observed. Aggregations of Langerhans granules and fusions of granules with LC plasma membranes were found exclusively at LC-keratinocyte interfaces. At LC-lymphocyte contact zones cell membrane appositions were seen. In all cases investigated, virus-like particles were mainly ound in LC and indeterminate cells (IDC). In 3 cases lymphocytes also contained these particles. It was of particular interest that virus-like particles were observed in skin specimens of all diseases investigated. Discrimination of these particles from other cellular organelles - especially lysosomes- was difficult, however. The significance of our findings, particularly regarding to the supposed virus aetiology of cutaneous T cell lymphomas, is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00695048
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  • 4
    Electronic Resource
    Electronic Resource
    Heavy chain loss after treatment with melphalan in a patient with “nonsecretory” myeloma (1983)
    Springer
    Annals of hematology 46 (1983), S. 73-80 
    Details
    ISSN: 1432-0584
    Keywords: Multiple myeloma-Plasma cell ; Electron microscopy ; Fluorescent antibody technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of “nonsecretory” myeloma is described. The patient had typical osteolytic lesions and marked infiltration of myeloma cells in the bone marrow, and plasma cell leukemia. A good partial remission was obtained with Melphalan, but the patient relapsed and died one year later. Immunofluorescent and immunoelectroscopic studies on the myeloma cells demonstrated the presence of cytoplasmic γ-and κ-chains at the initial stage and of only κ-chains at a relapse. The electron microscopic method for polysome analysis indicated that both L-and H-chains were synthesized on membrane-bound polysomes initially, but the ability to produce H-chain was missing at the relapse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00320661
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  • 5
    Electronic Resource
    Electronic Resource
    Quantitative light and electron microscopic changes in thymic reticular epithelial cells during moloney-virus-induced lymphoma development (1983)
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 102-111 
    Details
    ISSN: 1432-1335
    Keywords: Murine lymphoma development ; Virus infection ; Thymus ; Reticular epithelial cells ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report describes two types of reticular epithelial cell in the thymic cortex of the BALB/c mouse, an immature and a mature form. During early stages of lymphoma development, i.e., 2–6 weeks postinfection (p.i.) with Moloney leukemia virus (M-MuLV), activation of the epithelial cells is observed. Although the percentage of these cells in the total cell population of the thymic cortex remains constant during that time, the number of mature epithelial cells is significantly increased in infected animals. Subsequently, about 6 weeks p.i., the number of immature epithelial cells starts to increase, whereas the number of mature reticular epithelial cells declines and the appearance of the mature epithelial cells changes drastically. The results of light and electron microscopic studies indicate degeneration of the mature reticular epithelial cells at the onset of lymphoma development at a time when the first deficiencies in the immunologic competence of the reticular epithelial cells are apparent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00395387
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  • 6
    Electronic Resource
    Electronic Resource
    Biologic characterization of human bone tumors (1983)
    Springer
    Journal of cancer research and clinical oncology 106 (1983), S. 234-239 
    Details
    ISSN: 1432-1335
    Keywords: Osteosarcoma ; Collagen types ; Immunofluorescence microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixteen cases of typical highly malignant osteosarcoma were investigated by light, electron, and immunofluorescence microscopy to demonstrate the presence of collagen types I–III. It was shown that, in light-microscopically anaplastic areas of the tumor, collagen type III predominates, while only very few membranes of collagen type I are observed. Ultrastructurally, the cells are characterized by numerous free ribosomes in their cytoplasm and only a few membranes of granular endoplasmic reticulum (ER). In osteoblastic areas, collagen type I is increased, while type-III collagen is decreased. The cytoplasm of cells contains markedly more granular ER. An increasing mineralization of matrix is observed. In fibroblastic areas of the tumors, collagen types I and III are codistributed. Tumor cells have a fibroblast appearance with elongated nuclei and well developed granular ER. The chondroblastic areas, characterized by immature neoplastic cartilage, contain varying amounts of collagen type II. Chondroblast-like tumor cells have typical ring-shaped membranes of granular ER in their cytoplasm. The evidence of different collagen types in osteosarcomas lends additional support to the concept that a pluripotent mesenchymal cell is the stem cell of osteosarcomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402614
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  • 7
    Electronic Resource
    Electronic Resource
    The hemangioendothelioma of the thyroid (1983)
    Springer
    Virchows Archiv 400 (1983), S. 119-142 
    Details
    ISSN: 1432-2307
    Keywords: Thyroid neoplasms ; Hemangioendothelioma ; Electron microscopy ; Factor VIII-related antigen (FVIIIRAG) ; Tumour classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 65 cases of hemangioendothelioma (HE) of the thyroid were accepted as such after control of slides of surgical or autopsy specimen or both. In a few of the more recent cases material could be examined by electron microscope and in some the search for factor VIII-related antigen (FVIIIRAG) was carried out. The demonstration of Weibel-Palade bodies in tumour cells in two cases and the evidence of FVIIIRAG in tumour cells of at least two cases, including primary tumour and distant metastasis, finally show, that the hemangioendothelioma of the thyroid is not simply an anaplastic carcinoma with some peculiar features; at least some of these tumours are true endotheliomas. The proposal that the term hemangioendothelioma be eliminated from the classification of thyroid tumours is therefore unfounded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00585495
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  • 8
    Electronic Resource
    Electronic Resource
    Myxoid malignant fibrous histiocytoma versus myxoid liposarcoma (1983)
    Springer
    Virchows Archiv 400 (1983), S. 187-199 
    Details
    ISSN: 1432-2307
    Keywords: Malignant fibrous histiocytoma ; Liposarcoma ; Sarcoma ; Soft tissue neoplasms ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural comparison of 7 examples of myxoid malignant fibrous histiocytoma (myxoid MFH) with 6 of myxoid liposarcoma is described. Despite certain histological differences between the two, electron microscopy was more valuable in differentiating MFH from liposarcoma. Electron microscopically, MFH contained a variety of cell types including histiocyte-like, fibroblast-like, intermediate-type, xanthomatous, multinucleated tumor giant cells and undifferentiated cells. Liposarcoma was composed mainly of lipoblasts at various stages of differentiation with a minority of undifferentiated cells and fibroblast-like cells. In contrast to the component cells of the MFH, these lipoblasts were characterized by abundant cytoplasmic glycogen, numerous pinocytotic vesicles and a discontinuous basal lamina in addition to large lipid droplets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00585500
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  • 9
    Electronic Resource
    Electronic Resource
    Electron-microscopic examination of primary diffuse tracheobronchial amyloidosis (1983)
    Springer
    Virchows Archiv 400 (1983), S. 97-106 
    Details
    ISSN: 1432-2307
    Keywords: Tracheobronchial amyloidosis ; Electron microscopy ; Amyloid fibril ; Fibroblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The author reports on the electron-microscopic examination of the diffuse tracheobronchial amyloidosis of a 51-year-old patient. The amyloid deposits were located in the lamina propria of the tracheal and bronchial mucosa. At the edge of the nodular deposits, condensation and radial arrangement of amyloid fibrils could be seen. Closely connected with the amyloid, active fibroblasts were present and their cytoplasm contained amyloid fibrils. The cell membrane of the fibroblasts was missing in part. Intracellular amyloid fibrils mingled with extracellular deposits. It can be assumed that active fibroblasts play an important role in local amyloid formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00627013
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  • 10
    Electronic Resource
    Electronic Resource
    Mitochondrial abnormalities in Menkes' kinky hair disease (MKHD) (1983)
    Springer
    Acta neuropathologica 59 (1983), S. 295-303 
    Details
    ISSN: 1432-0533
    Keywords: Menkes' kinky hair disease ; Brain degeneration ; Mitochondrial abnormalities ; Distribution ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain of an autopsy case of Menkes' kinky hair disease (MKHD), after routine histological examination, was studied extensively by electron microscopy, particularly the mitochondrial alterations. There were widespread mitochondrial abnormalities, including enlargement with tubulo-vesiculated cristae, swelling, and dense body formation and occasional accumulation of glycogen within mitochondria, in addition to increased numbers of mitochondria in some neurons. These abnormalities of mitochondria were present in decreasing severity in the following: Purkinje cells, neurons of the molecular and granule cell layers of the cerebellum, and neurons of the cerebral cortex, globus pallidus, lateral nuclei of the thalamus, caudate nucleus, and the myelinated axons in the white matter. This distribution and the degree of mitochondrial abnormalities in the various structures of the brain were compared with those of degenerative lesions in the respective structures. The comparison disclosed that there was a positive correlation between the two. The mitochondrial enlargement and swelling as in the present study had been well documented in the brain of the brindled mouse; mitochondrial dense bodies had also been reported in previous case reports of MKHD by other authors. The present study strongly suggests that the mitochondrial disease is an essential abnormality and may be responsible for the progressive degeneration of the CNS in MKHD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691496
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  • 11
    Electronic Resource
    Electronic Resource
    Sural nerve biopsies from workers with a history of chronic exposure to organic solvents and from normal control cases (1983)
    Springer
    Acta neuropathologica 62 (1983), S. 73-86 
    Details
    ISSN: 1432-0533
    Keywords: Human sural nerve ; Electron microscopy ; Myelin sheath thickness ; Internodal length ; Node of Ranvier ; Organic solvents ; Glycogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural and morphometric study was performed on sural nerve biopsies of four industrial spray painters (35–59 years) and 11 controls (6–64 years). No difference could be shown in spray painters and age-matched controls as to the number of myelinated nerve fibres per area, their size distribution, variation of internodal length along single nerve fibres or the ratio between the number of myelin lamellae and the axon circumference. There was marked scattering of the two latter parameters in older exposed and control individuals. The distribution of NADH2-tetrazolium reductase activity was similar in exposed and control cases. The general ultrastructural appearance of nodal-paranodal regions in controls conformed with that noted in experimental animals. The overall ultrastructural organization and age-related changes of nerves of exposed cases were similar to those of control cases except for a presence of paranodal axonal mitochondria which contained glycogen-like particles in exposed cases. In one exposed case abundant dispersed or clustered glycogen-like particles were seen in the paranodal axoplasm. These findings are suggested to be an effect of chronic exposure to organic solvent vapours. Ageing seems, however, to have a much greater impact on the morphology of the sural nerve fibre than occupational exposure to organic solvent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684923
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  • 12
    Electronic Resource
    Electronic Resource
    Ultrastructural abnormalities of muscle and neuromuscular junction differentiation in a bovine congenital neuromuscular disease (1983)
    Springer
    Acta neuropathologica 62 (1983), S. 112-120 
    Details
    ISSN: 1432-0533
    Keywords: Motor end-plates ; Abnormal differentiation of motor end-plates ; Arthrogryposis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The syndrome of arthrogryposis and palatoschisis (SAP), an inherited syndrome of muscular hypotonia in Charolais cattle, was used as an experimental model to study neuromuscular differentiation. The ultrastructural development of muscle, peripheral nerve, and neuromuscular junctions was studied to determine the sequence of events preceding hypotrophic changes in the skeletal muscles of affected calves at birth. Dorsiflexion of the metatarsophalangeal joints in the hindlimbs occurred in fetuses older than 3 months of age, but hypotrophic changes in skeletal muscle, manifested as small fibers scattered among larger and occasional degenerating fibers, was not apparent until late in gestation, affecting 8-month-old fetuses and neonatal calves. Electron microscope and enzyme histochemistry studies disclosed differentiation of skeletal muscle into fiber types which is consistent with changes expected from disuse and does not indicate a primary myopathic abnormality. Abnormal differentiation of neuromuscular junctions (NMJ), composed of several separated axonal endings terminating in shallow synaptic gutters, indicated impaired maturation of the synapse. The earliest indication of abnormal NMJ was observed in a 5-month-old SAP fetus. The clinical signs and pathologic changes found in the neuromuscular junction and skeletal muscle of SAP fetuses are consistent with an embryologic defect occurring during development of the central nervous system (CNS) that affects the integrated function of the motor neurons to the limbs. However, diversification of myofibers by histochemistry and ultrastructural parameters is evidence that the intrinsic physiologic properties of spinal motor neurons were retained.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684927
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  • 13
    Electronic Resource
    Electronic Resource
    Electron-microscopical study of a Rathke's cleft cyst (1983)
    Springer
    Acta neuropathologica 60 (1983), S. 14-18 
    Details
    ISSN: 1432-0533
    Keywords: Rathke's cleft cyst ; Craniopharyngioma ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The electron-microscopical appearance of a Rathke's cleft cyst is described. The cyst lining is seen to consist predominantly of secretory columnar epithelium, both ciliated and non-ciliated. There are also epidermoid cells occurring singly or in squames. The histogenesis of Rathke's cleft cysts, in relation to craniopharyngiomas, is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685342
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  • 14
    Electronic Resource
    Electronic Resource
    Methylmercury poisoning of the developing nervous system: Morphological changes in neuronal mitochondria (1983)
    Springer
    Acta neuropathologica 61 (1983), S. 116-122 
    Details
    ISSN: 1432-0533
    Keywords: Methylmercury ; Mitochondria ; Cerebral cortex ; Postnatal development ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neonatal rats received s.c. injections of methymercuric chloride (MeHg) in physiological saline (1.5 mg Hg/kg b.wt.) at 48-h intervals from postnatal day 2 to day 50. Littermate controls were injected with an equivalent volume of saline. All animals were perfused on day 51 and blocks of cerebral cortex were prepared for electron microscopy. Ultrastructural changes in mitochondria were evident in the dendrites, axons and presynaptic terminals of cortical neurones in the MeHg-treated animals. Many mitochondria were condensed with an increased electron density of the inner matrix. Some profiles exhibited regressive alterations, including a disruption of cristae and the inner membrane with an accumulation of electron-opaque material in the matrix. Membranous whorls were found in association with the most degenerate mitochondria. A morphometric analysis of mitochondrial profiles in the neuropil of layer I revealed a 24% decrease in average profile area and a 16% increase in the number of profiles per micrograph in the MeHg-treated animals. These pathological changes in mitochondrial ultrastructure are consistent with an inhibition of mitochondrial respiration. The observed increase in the number of mitochondrial profiles may reflect a compensation by cortical neurons for the reduced efficiency of aerobic metabolism in the individual organelle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00697390
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  • 15
    Electronic Resource
    Electronic Resource
    Zur feinstruktur intrafusaler und extrafusaler Nervenabschnitte der Rattenmuskelspindel nach Ischiadicusdurchtrennung (1983)
    Springer
    Acta neuropathologica 59 (1983), S. 246-254 
    Details
    ISSN: 1432-0533
    Keywords: Muscle spindle ; Electron microscopy ; Terminal nerves ; Denervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intrafusal and extrafusal nerve segments in muscle spindles from tumbricalis muscles of the hind-paw of the rat were studied by electron microscopy from 10h to 5 days after severance of the sciatic nerve. In several spindles examined, nerve fascicles piercing the spindle capsule in the equatorial region contained a large myelinated, a smaller myelinated and an unmyelinated fiber. Unmyelinated fibers were not present in small fascicles leading to the polar region. The changes in the extrafusal nerve segments followed the pattern of Wallerian degeneration. Intra-axonal glycogen deposits were prominent in sensory fibers. The unmyelinated fibers were the earliest to degenerate, the large myelinated ones the latest. Differences between motor and sensory fiber degeneration emerged in their preterminal intrafusal segments and were analogous to those of the nerve endings. Terminal nerve fibers in the spindle equator succumbed to attack of mesenchymal cells, leaving extensive basement membrane reduplications around myelin debris-laden Schwann cells, while polar fibers were engulfed by Schwann cell processes, leaving regular bands of Büngner.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691489
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  • 16
    Electronic Resource
    Electronic Resource
    Adrenoleukodystrophy-cerebello-brainstem dominant case (1983)
    Springer
    Acta neuropathologica 60 (1983), S. 149-152 
    Details
    ISSN: 1432-0533
    Keywords: Adrenoleukodystrophy ; Cerebello-brainstem involvement ; Electron microscopy ; Biochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of adrenoleukodystrophy was studied morphologically and biochemically. The patient was a 28-year-old man with no family history of adrenoleukodystrophy. His neurologic symptoms were cerebellar ataxia, spastic paraplegia, pseudo-bulbar palsy, and a minimal visual disturbance, with neither adrenal nor hypogonadal symptoms. The morphological and biochemical findings in this case are identical with those in typical adrenoleukodystrophy, but the topographical distribution of the lesions is distinctly different. The changes selectively affect the white matter in the cerebellum and brain stem in contrast to minimal involvement of the occipital white matter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685361
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  • 17
    Electronic Resource
    Electronic Resource
    Hirano body in extraocular muscle (1983)
    Springer
    Acta neuropathologica 60 (1983), S. 309-313 
    Details
    ISSN: 1432-0533
    Keywords: Hirano bodies ; Extraocular muscle ; Aging ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-three rectus superior extraocular muscles from 23 autopsy cases, all over 60 years, were examined. Eosinophilic inclusions (Hirano bodies) were observed in all the muscles; they were stained deep red by Masson's trichrome stain and were positive for protein stain. They consisted of a collection of filamentous structures of two types: (1) a regular array of filaments 100 Å in diameter which sometimes were arrayed in perpendicular planes and (2) another type in a herring bone or ladder-like pattern. Both structures were closely associated with the accumulated thin filaments 50–60 Å in diameter (actin?) in the subsarcolemma. The frequent appearance in aged muscle fibers of Hirano bodies indicates that their formation is a change closely related with aging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691883
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  • 18
    Electronic Resource
    Electronic Resource
    Glycogen accumulations in differentiating mesonephric ducts and tubuli in male human embryos (1983)
    Springer
    Anatomy and embryology 168 (1983), S. 445-453 
    Details
    ISSN: 1432-0568
    Keywords: Electron microscopy ; Mesonephric duct ; Fetus ; Glycogen ; Human development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human mesonephric duct epithelial cells contained empty appearing regions in the infranuclear cytoplasm when prepared for transmission electron microscopy using glutaraldehyde and osmium fixation. The same regions stained positively with PAS in Epon sections for light microscopy suggesting that glycogen was present. Incubation with saliva abolished the reaction. For electron microscopy the glycogen stained very intensely if a mixture of osmium tetroxide and potassium ferrocyanide was used instead of osmium alone. Glycogen accumulations were present between the ages of 5 to 10 weeks and absent at the age of 15 weeks. Reports by others indicate that glycogen may be present in different reactive forms in relation to its staining behaviour after various fixatives. The present results, and similar studies in other tissues, indicate that osmium tetroxide-potassium ferrocyanide fixative should be used routinely for preservation of embryos and fetuses and where indicated, for ultrastructural identification of glycogen and cytoplasmic filaments in clinical specimens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304280
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  • 19
    Electronic Resource
    Electronic Resource
    Ultrastructural demonstration of Fcγ-receptors in sarcoid skin lesions (1983)
    Springer
    Archives of dermatological research 275 (1983), S. 156-158 
    Details
    ISSN: 1432-069X
    Keywords: Sarcoidosis ; Fcγ-receptors ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP were used to study the Fcγ-receptors in granulomas of cutaneous sarcoidosis. Cryostat sections of skin biopsies were incubated with HRP-anti-HRP, and the peroxidase activity was demonstrated with 3,3-diaminobenzidine tetrahydrochloride and H2O2. Most cells in the granulomas, both epithelioid and giant cells, were stained. By electron microscopy, the reaction products were localized to the plasma membranes of the cells as well-defined granular deposits. No reaction product was demonstrated intra- or extracellularly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00510046
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  • 20
    Electronic Resource
    Electronic Resource
    ATPase, antigens detected by monoclonal antibodies, ultrastructural characters: which is the best marker for langerhans cells? (1983)
    Springer
    Archives of dermatological research 275 (1983), S. 407-411 
    Details
    ISSN: 1432-069X
    Keywords: Langerhans cell ; ATPase ; Ia-like antigen ; OKT6 ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417343
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  • 21
    Electronic Resource
    Electronic Resource
    Subependymal giant-cell tumor: Astrocytic or neuronal? (1983)
    Springer
    Acta neuropathologica 60 (1983), S. 271-277 
    Details
    ISSN: 1432-0533
    Keywords: Tuberous sclerosis ; Subependymal giant-cell tumor ; Immunohistochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue from seven patients with tuberous sclerosis and subependymal giant-cell tumors was examined with special stains, immunohistochemistry, and electron microscopy. Immunoreactive glial fibrillary acidic protein (GFAP) was not found in the giant cells of four tumors, but was present in some tumor cells in the other three. Immunoreactive S-100 protein was present in tumor cells of six cases; it was also seen in more tumor cells than was GFAP. Electron microscopy was similar in all cases and showed that the tumor cells had numerous organelles — many dense bodies thought to be primary lysosomes, swollen mitochondria, Golgi complexes, rough and smooth endoplasmic reticulum, free ribosomes, and sparsely distributed intermeadiate filaments. In one case, neurosecretory granules, microvilli, and synapses were observed. In another subject, prominent, thick bundles of glial filaments were seen. These findings suggest that the tumor is made up of unique cells in addition to cells with recognizable neuronal or astrocytic features.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691876
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  • 22
    Electronic Resource
    Electronic Resource
    Bubbles and hematologic alterations in intracranial veins during experimental decompression sickness (1983)
    Springer
    Acta neuropathologica 59 (1983), S. 139-144 
    Details
    ISSN: 1432-0533
    Keywords: Decompression sickness ; Brain ; Gas bubbles ; Blood-bubble interface ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were exposed to 6.1 bar (abs.) air for 90 min and subsequently decompressed to the ambient pressure. After a decompression rate of 6.8 bar/min pial veins and superior sagittal sinuses were found to contain gas bubbles; no intravascular bubbles were observed subsequent to a decompression rate of 1.5 bar/min. Under the electron microscope platelet aggregates were observed at both the electron-dense layer of the blood-bubble interface and in pial veins with no bubbles. It is concluded that during decompression sickness bubbles and both activation and aggregation of platelets occur in intracranial veins. Subsequent venous congestion may contribute to the neuronal lesions and symptoms of acute decompression sickness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00691600
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  • 23
    Electronic Resource
    Electronic Resource
    Pityriasis rubra pilaris: A clinico-pathological and therapeutic study with special reference to histochemistry, autoradiography, and electron microscopy (1983)
    Springer
    Archives of dermatological research 275 (1983), S. 287-295 
    Details
    ISSN: 1432-069X
    Keywords: Pityriasis rubra pilaris ; Histochemistry ; Autoradiography ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five patients with pityriasis rubra pilaris (PRP) were analyzed by means of light and electron microscopy as well as by histochemistry and autoradiography. The results were compared with findings in psoriasis vulgaris. In PRP we found a moderate increase of the labeling index of epidermal cells, a highly increased labeling index of dermal infiltrating cells, and a mild spongiosis, and in the stratum granulosum, a decreased number of tonofilaments and an increased number of keratinosomes. The horny layer in PRP showed a pronounced histochemical and electron microscopical parakeratosis, even when histological parakeratosis was absent. In contrast with psoriasis vulgaris, there was no exocytosis of polymorphonuclear leucocytes into the epidermis, the papillomatosis index was normal, and there were no tortuous capillaries in the dermal papillae. The stratum granulosum was always present and sometimes thickened, showing electron microscopical changes different from those referred to in psoriasis. These changes point to a relatively distinct pattern of epidermal changes in PRP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00417199
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  • 24
    Electronic Resource
    Electronic Resource
    Two types of intracytoplasmic inclusions in the cells of a patient with acute lymphoblastic leukemia (1983)
    Springer
    Annals of hematology 47 (1983), S. 13-19 
    Details
    ISSN: 1432-0584
    Keywords: Acute lymphoblastic leukemia ; Intracytoplasmic inclusions ; Mitochondria ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A patient with acute lymphoblastic leukemia (ALL) with cells containing two types of cytoplasmic inclusions is described. The inclusions appeared as glubular bodies containing electron dense material with homogenous structure and as crystalloid formations confined in organelles with structure similar to that of the surrounding mitochondria. In distinction to other reports, these structures were not related to the endoplasmic reticulum. The possibility that some of them represented altered mitochondria is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00321046
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  • 25
    Electronic Resource
    Electronic Resource
    The bioavailability of circulating antibody-bound insulin following insulin withdrawal in Type I (insulin-dependent) diabetes (1983)
    Springer
    Diabetologia 24 (1983), S. 355-358 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; insulin ; insulin antibody ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin withdrawal studies were performed in 12 Type 1 (insulin-dependent) C-peptide negative diabetic patients with low to moderate insulin antibody levels, to assess the biological availability of antibody-bound insulin and its clinical significance. There was a highly significant correlation between the extent to which the free insulin concentration was maintained during the period of insulin withdrawal and both the level of insulin-binding by serum and the total insulin concentration at the start of the study. During insulin withdrawal, the patients who best maintained their circulating free insulin levels showed the smallest increases in blood glucose and 3-hydroxybutyrate concentrations. We conclude that antibody-bound insulin is available for physiological action, and that in those individuals with moderate antibody concentrations it is capable, in the fasting state, of maintaining free insulin levels. In these circumstances insulin antibodies are behaving as simple carrier proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00251824
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  • 26
    Electronic Resource
    Electronic Resource
    Pharmacodynamic and pharmacokinetic evaluation in man of the new sympathomimetic amezinium (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 185-190 
    Details
    ISSN: 1432-1041
    Keywords: amezinium ; hypotension ; antihypotensive drug ; ECG ; concentration-effect relationship ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood pressure, ECG and plasma concentration were determined for up to 12h following single i.v. (10 mg) and oral (20 mg) doses of amezinium (Regulton®) in 8 healthy, male volunteers. The i.v. and oral doses were almost equi-active in significantly increasing systolic blood pressure (SBP) by 14.5 and 15.6 mmHg, respectively. The maximum SBP after the i.v. dose was reached after 45 min, and 105 min after oral administration. The heart rate fell reflexly. The increases in mean and diastolic blood pressures were not significant. Pulse pressure was enhanced after both i.v. and oral administration. The effect on systolic blood pressure lasted for about 4 h. There was a slight shortening of the QTc duration, which could not be explained as a drug effect. Other ECG time intervals were not altered. Multiple regression analysis showed a significant positive correlation between the log plasma concentration and the increase in SBP between 0.5 and 5 h after oral administration (r=0.78,p〈0.001) and between 0.75 and 5 h after i.v. administration (r=0.83,p〈0.001). 30 min after amezinium p.o. the mean SBP began to rise, when a plasma level of about 30 ng/ml was reached.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613815
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  • 27
    Electronic Resource
    Electronic Resource
    Plasma levels of sulfinpyrazone and of two of its metabolites after a single dose and during the steady state (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 231-235 
    Details
    ISSN: 1432-1041
    Keywords: sulfinpyrazone ; pharmacokinetics ; metabolites ; inhibition of platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulfinpyrazone, and the plasma levels of its sulfide and sulfone metabolites, have been determined after a single oral dose (400 mg) and during steady-state conditions (4×200 mg daily for 6 days) in healthy female volunteers. The plasma half-lives of sulfinpyrazone, the sulfone and the sulfide were 3.7, 3.2 and 14.7 h, respectively, during steady-state. After a single dose and during steady state conditions the half-lives of sulfinpyrazone and the sulfone did not differ significantly. The trough plasma levels of the sulfide metabolite exceeded those of the parent compound in four of the six volunteers on the last day of the study. The data suggest that in man the most likely candidate for the prolonged inhibition of platelet aggregation observed after treatment with sulfinpyrazone is its sulfide metabolite, because of its prolonged elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613823
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  • 28
    Electronic Resource
    Electronic Resource
    Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 267-271 
    Details
    ISSN: 1432-1041
    Keywords: trimethoprim ; sulphadiazine ; urinary tract infection ; children ; pharmacokinetics ; urinary concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2–56 months. A suspension of TMP-SD (9+41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9–3.7 mg/kg/day) and SD (12.9–16.7 mg/kg/day) were also given to children of different ages. After 2–4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 µg/ml and 27 µg/ml, respectively, were found within 2–4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613830
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  • 29
    Electronic Resource
    Electronic Resource
    Pharmacodynamic and pharmacokinetic interactions between ketamine and diazepam (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 337-343 
    Details
    ISSN: 1432-1041
    Keywords: ketamine ; diazepam ; drug interaction ; pharmacokinetics ; premedication ; clorazepate ; drug metabolism ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Anaesthesia with continuous i.v. ketamine and 65% nitrous oxide in oxygen was given to a total of 49 patients undergoing major abdominal surgery. A control group was premedicated with atropine and other groups received in addition rectal diazepam or clorazepate i.v. Four further patients had been on oral diazepam or barbiturates for 1–14 years; as premedication they received atropine alone. The anaesthetic technique gave good operative conditions in the 4 groups of patients. The haemodynamic stimulation of ketamine was significantly reduced in patients premedicated with diazepam. Psychotomimetic side effects were not prominent in any of the groups. Patients premedicated with diazepam required a lower rate of ketamine infusion as compared to controls during the initial 30 min of anaesthesia. The patients in the other groups did not differ from the control group in this respect. There were large differences in metabolic pattern between the groups. As compared to the controls, the patients on long-term diazepam or barbiturates had high concentrations of hydroxylated metabolites, with levels higher than that of norketamine. The patients pretreated with diazepam had very low plasma levels of hydroxylated metabolites. Clorazepate premedication did not significantly affect the metabolism of ketamine. The biological half-life of ketamine was significantly increased in the diazepam-treated group, and it was shortened in those on long term treatment with barbiturates or diazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610051
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  • 30
    Electronic Resource
    Electronic Resource
    Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 485-494 
    Details
    ISSN: 1432-1041
    Keywords: amiodarone ; pharmacokinetics ; therapeutic serum level ; thyroid function ; antiarrhythmic therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 µmol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 µmol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 µmol/l. Tentatively, a therapeutic range of 1.5 to 4 µmol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609891
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  • 31
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sotalol during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    Details
    ISSN: 1432-1041
    Keywords: sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609896
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  • 32
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of biliary excretion in man V (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 549-556 
    Details
    ISSN: 1432-1041
    Keywords: dibromosulfophthalein ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; biliary fistula ; enterohepatic circulation ; hepatic transport test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of dibromosulfophthalein (DBSP), the 3,6-dibromo analogue of BSP, was studied in 7 patients with a biliary fistula, 52 h after cholecystectomy, and in 6 gynaecological patients with an indwelling urethral catheter, following extirpation of the uterus i.e. with an intact enterohepatic circulation. Plasma protein binding determined by ultrafiltration was 98–99% up to a concentration of 700 µg/ml. After an intravenous bolus injection of DBSP 5 mg/kg, a biexponential plasma decay was found in both groups, with a rapid initial t1/2 of 2–6 min and a slow secondary phase of 33–109 min (mean 66 min) in the cholecystectomy patients, and 10–30 min (mean 19 min) in the gynaecological patients. The biliary excretion rate varied considerably between the patients and was highly correlated with bile flow. Biliary output amounted to a maximum of 86% of the dose in 24 h. The excretion rate curves showed ascending and descending phases, the mean terminal t1/2 being 65 min. Urinary excretion was 3–11% of the dose in 8 h in the gynaecological patients (mean 6%) and 6–31% in the cholecystectomy group (mean 16%). Renal clearance of unbound DBSP was about ten-times greater than the glomerular filtration rate, which indicates tubular secretion. A two compartment model with elimination from the peripheral and central compartments was selected because of these data. Analysis of the plasma-disappearance curves indicated an initial plasma clearance of 500–600 ml/min, which suggests that hepatic uptake will be very dependent on flow. Steady state (biliary) clearance was about 400 ml/min in the gynaecological group and approximately half that in the cholecystectomy patients; V1 tended to be higher and V2 to be lower in the latter group. It is concluded that biliary excretion rate of DBSP in patients with a biliary fistula is probably depressed by the postoperative bile drainage and the lack of enterohepatic cycling of bile salts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609902
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  • 33
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of hydrochlorothiazide in relation to renal function (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 661-665 
    Details
    ISSN: 1432-1041
    Keywords: hydrochlorothiazide ; pharmacokinetics ; renal failure ; dosage adjustment ; excretory mechanism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542218
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  • 34
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of subcutaneous dihydroergotamine with and without a dextran 70 infusion (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 813-818 
    Details
    ISSN: 1432-1041
    Keywords: dihydroergotamine ; dextran 70 ; pharmacokinetics ; radioimmunoassay ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of subcutaneous dihydroergotamine (DHE) with or without dextran 70 infusion was evaluated in a single- and multiple-dose study in 30 patients. Radioimmunoassay was used to measure plasma DHE and the anthrone method to determine the dextran concentration. In the single-dose study no significant interaction between DHE and dextran was noted with respect to their plasma levels. The absorption of s.c. DHE was rapid and the disappearance curve followed a biphasic pattern, t0.5 α being 1.4 and 2.0 h, t0.5 β 22 and 21 h for DHE and DHE/dextran 70, respectively. In the multi-dose study the trough level of DHE initially had a tendency to rise, in accordance with simulated plasma concentration curves. DHE trough levels were about 0.5 ng/ml and were well above the assumed minimum effective value to induce venoconstriction (0.06 ng/ml). Dextran concentrations were significantly higher when DHE was co-administered, possibly, due to changes in plasma volume. It is concluded that DHE 0.5 mg s.c. twice daily will give an adequate plasma concentration and that there was no important interaction between it and infused dextran 70.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607093
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  • 35
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of the new analgesic, meptazinol, after oral and intravenous administration to volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: meptazinol ; pharmacokinetics ; multiple dosing ; plasma protein binding ; analgesic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of meptazinol (Meptid®) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vdβ) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean=8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544019
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  • 36
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and absolute bioavailability of carteolol, a new β-adrenergic receptor blocking agent (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 95-101 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544023
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  • 37
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of triamterene after i.v. administration to man: Determination of bioavailability (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    Details
    ISSN: 1432-1041
    Keywords: triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543797
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  • 38
    Electronic Resource
    Electronic Resource
    On the pharmacokinetics of pengitoxin and its cardioactive derivative 16-acetyl-gitoxin (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 369-373 
    Details
    ISSN: 1432-1041
    Keywords: pengitoxin ; pharmacokinetics ; 16-acetylgitoxin ; absorption ; urinary excretion ; healthy subjects ; cardiac glycoside
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pengitoxin has been studied in 28 healthy subjects after intravenous and oral administration. The mean plasma concentration 24 h after 0.5 mg i.v. was 5.2 ng · ml−1. Following an open two-compartment model a mean elimination half-life of 60.5 h (24.9 to 103.5 h) and a mean volume of distribution (Vdarea) of 66.91 (31.8 to 109.61) were calculated. Absorption calculated by comparison of the AUC0-∞-values amounted to 99%. Within 4 days, 16.7% (11.7 to 21.1%) or 27.8% (18.4 to 33.7%) (0.5 mg i.v. or 1.2 mg p.o.) was excreted in urine. After pengitoxin 0.5 mg i.v. total body clearance and renal clearance were 13.3 ml · min−1 (7.0 to 18.6 ml · min−1) and 3.0 ml · min−1 (1.9 to 3.9 ml · min−1) respectively. The elimination half-life of pengitoxin is longer than that of digoxin and distinctly shorter than that of digitoxin, whilst its distribution volume and clearance are closer to those of digitoxin than of digoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037950
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  • 39
    Electronic Resource
    Electronic Resource
    Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding I. Theoretical considerations (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 399-405 
    Details
    ISSN: 1432-1041
    Keywords: ceftriaxone ; pharmacokinetics ; concentration-dependent binding ; volume of distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have theoretically examined the influence of plasma protein binding (specifically the fraction unbound, fp) on the pharmacokinetic parameters following rapid injection of a drug undergoing concentration-dependent binding. Particular emphasis was placed on the apparent volume of distribution terms based on both total and unbound drug concentrations. Computer simulations were performed to establish the validity and utility of such relationships. The following observations were made: a) distributional parameters based on total drug (both Vβ and the model-independent VSS) were inaccurate/invalid; b) V β based on unbound drug was misleading; c) the model-independent VSS for unbound drug accurately predicted the steady state situation. Furthermore, two new terms ( $$\bar f_P $$ and $$\bar V_{SS}^T $$ ) were introduced which provide additional insight concerning the disposition of this type of drug. The $$\bar f_P $$ is the area-weighted average fraction unbound in the plasma and $$\bar V_{SS}^T $$ is the corrected steady state distribution term for total drug levels. The present study indicates that useful distributional and clearance terms can be calculated for this type of drug, provided that the time course of unbound drug as well as total drug can be followed. Moreover, guidelines for their extrapolation to steady state conditions and their correct interpretations are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037955
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  • 40
    Electronic Resource
    Electronic Resource
    Rapid achievement of a serum concentration plateau of digoxin through controlled infusion (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 455-457 
    Details
    ISSN: 1432-1041
    Keywords: digoxin ; concentration plateau ; pharmacokinetics ; systolic time intervals ; optimal infusion scheme ; dose-response data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Using a volume-controlled infusion pump, a mean serum plateau level of digoxin of 4–5 ng/ml was rapidly achieved and maintained in 6 healthy volunteers. The infusion scheme was calculated on the basis of data published on the pharmacokinetics and pharmacodynamics of digoxin following bolus intravenous injection. The magnitude of the response (change in electromechanical systole) at the end of the plateau phase was comparable to that observed with the concentration in the therapeutic range at steady state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542110
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  • 41
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    Details
    ISSN: 1432-1041
    Keywords: canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542109
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  • 42
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of methadone in methadone maintenance treatment: Characterization of therapeutic failures (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 497-501 
    Details
    ISSN: 1432-1041
    Keywords: methadone ; pharmacokinetics ; steady state ; addiction rehabilitation ; therapeutic failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the β-phase (t1/2β), volume of distribution during the postdistributive phase (Vdβ) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vdβ and Vdss were found between the two groups. The therapeutic failures had a smaller Vdβ and Vdss 3.09±0.96 l/kg and 2.74±0.96 l/kg vs 4.56±1.00 l/kg and 4.20±0.78 l/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2β — 24.5±2.6 h in the therapeutic failures and 34.0±7.0 h (p〈0.001) in the comparison group. However, the change in t1/2β was probably a consequence of the change in Vdβ, as the body clearance of M was similar in the two groups — 104±36 ml/min vs 111±36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval. The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage interval. Alternatively, a longer-acting opiate, such as 1-α-acetylmethadol (LAAM), may be used.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542117
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  • 43
    Electronic Resource
    Electronic Resource
    Pharmacodynamic and pharmacokinetic study of oral and intravenous penbutolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 529-534 
    Details
    ISSN: 1432-1041
    Keywords: penbutolol ; pharmacokinetics ; blood pressure effect ; heart rate effect ; dose response relationship ; tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The present study was done to establish the dose-response relationships for effects on heart rate and systolic and diastolic blood pressure, tolerance and plasma disappearance kinetics after large intravenous and oral doses of penbutolol. Twelve healthy volunteers were randomly allocated to receive penbutolol (n=8) or placebo (n=4) in this single blind, placebo-controlled investigation. The degree of beta-blockade was measured by standarized exercise tests at work loads selected to produce a heart rate of 150/min without treatment. Penbutolol was given as single i.v. doses of 3, 6 and 12 mg and as 40, 80 and 120 mg once daily for one week, measurements being made 2 and 24 h after the last dose. Penbutolol i.v. did not influence the resting heart rate but it did reduce resting systolic blood pressure in a non-dose dependent manner. Exercise heart rate and systolic pressure were lowered by all the intravenous doses. All oral doses of penbutolol lowered exercise heart rate and systolic blood pressure to the same extent. The reductions in exercise tachycardia was still present after 24 h. After i.v. administration t1/2 was approximately 1.2 h and the volume of distribution was 32–42 l. All doses were well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542123
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  • 44
    Electronic Resource
    Electronic Resource
    Relationships between several pharmacokinetic parameters and psychometric indices of subjective effects of Δ9-tetrahydrocannabinol in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 633-637 
    Details
    ISSN: 1432-1041
    Keywords: delta-9-tetrahydrocannabinol ; mood ratings ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study explored the relationships in man between various pharmacological effect of Δ9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective “high” rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, “high”). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective “high” rating, rather than other ratings more specific for particular moods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542351
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  • 45
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of digoxin in pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 117-121 
    Details
    ISSN: 1432-1041
    Keywords: serum digoxin ; pregnancy ; digoxin-renal-clearance ; creatinine-clearance ; digoxin-elimination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Digoxin-renal-clearance, creatinine-clearance, 24-h urine elimination of digoxin and serum digoxin were studied in 15 patients in the third trimester of pregnancy and 6 to 12 weeks post-partum. There was significant fall post-partum in the first three. There was also a significant fall post-partum in serum digoxin levels. This finding was unexpected, but may be due to heightened absorption exceeding increased elimination because of the physiological status in pregnancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544027
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  • 46
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of theophylline in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 89-92 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; kwashiorkor ; marasmus ; children ; nutritional status ; pharmacokinetics ; dosage recommendation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of theophylline in Ethiopian children of differing nutritional status was studied. In 8 children of normal weight, the t1/2β (4.93 h) plasma clearance (1.22 ml/min/kg and Vd area (504 ml/kg) were similar to those of Swedish children of normal weight. In children with marasmus or kwashiorkor there was an increased volume of distribution. The increase in Vd was reflected in an increased biological half-life, in spite of a slight but not significant increase in clearance in both of these groups of children. The pharmacokinetic changes in clearance and volume of distribution found in malnutrition should counteract each other, so from a clinical point of view theophylline can be given to Ethiopian children according to the standard dosage recommendation, regardless of nutritional status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613932
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  • 47
    Electronic Resource
    Electronic Resource
    Bioavailability and pharmacokinetics of theophylline in plain uncoated and sustained-release dosage forms in relation to smoking habit I. Single dose study (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 79-87 
    Details
    ISSN: 1432-1041
    Keywords: theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613931
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  • 48
    Electronic Resource
    Electronic Resource
    Bioavailability of oral dexamethasone during high dose steroid therapy in neurological patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    Details
    ISSN: 1432-1041
    Keywords: dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613935
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  • 49
    Electronic Resource
    Electronic Resource
    Elimination of cefroxadine (CGP-9000) from patients undergoing dialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 109-112 
    Details
    ISSN: 1432-1041
    Keywords: cefroxadine ; haemodialysis ; pharmacokinetics ; terminal renal impairment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions. The antibiotic was administered as a single oral dose of 500 mg. Cefroxadine followed a single compartment open kinetic model. During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 µg/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function. The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions. The average extraction coefficient was 0.249. It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613936
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  • 50
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of levonorgestrel in Indian women (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 255-259 
    Details
    ISSN: 1432-1041
    Keywords: levonorgestrel ; nutritional status ; combination pill ; pharmacokinetics ; indian women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A low dose combination pill containing levonorgestrel 150 µg and ethynylestradiol 50 µg was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The π t1/2 was lower in Group A women and the α-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (β t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613828
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  • 51
    Electronic Resource
    Electronic Resource
    Doxorubicin and 5-fluorouracil plasma concentrations and detectability in parotid saliva (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 261-266 
    Details
    ISSN: 1432-1041
    Keywords: doxorubicin ; 5-fluorouracil ; pharmacokinetics ; parotid saliva ; plasma concentration ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50–90 mg doxorubicin or 600–1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613829
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  • 52
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of melphalan in patients with multiple myeloma: An intravenous/oral study using a conventional dose regimen (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 283-285 
    Details
    ISSN: 1432-1041
    Keywords: melphalan ; myeloma ; pharmacokinetics ; i.v. dosing ; oral dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of melphalan have been studied after intravenous and oral dosing (10 mg) in 6 patients with multiple myeloma. After intravenous administration, mean plasma t0.5α was 8.0±2.3 min, t0,5β was 63.3±8.7 min, and total systemic clearance was 510.4±57.9 ml/min. After oral administration, the drug was rapidly absorbed (lagtime=18.4±3.7 min, absorption rate constant=0.0547±0.0166 min−1, Tmax=59.3±6.6 min), but there was considerable variation in its bioavailability (61.5−102.0% mean 78.3±6.3%). Variability in drug absorption may be responsible, at least in part, for variation in response to this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613833
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  • 53
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of oxmetidine, a new histamine H2-receptor antagonist, after single oral and intravenous doses (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 353-356 
    Details
    ISSN: 1432-1041
    Keywords: oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610054
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  • 54
    Electronic Resource
    Electronic Resource
    Analytical model of some pharmacokinetic and pharmacodynamic properties of fazadinium in man (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 407-413 
    Details
    ISSN: 1432-1041
    Keywords: neuromuscular blockade ; fazadinium ; pharmacokinetics ; pharmacodynamics ; predictive model ; receptor occupation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The neuromuscular blocking characteristics and plasma concentration decay of fazadinium bromide, a short acting, non-depolarizing muscular relaxant, were simultaneously observed under standardised conditions in 6 healthy, anaesthetized, adult patients. The results were analyzed by a new pharmacodynamic model, which takes into account certain relationships describing the binding of non-depolarizing neuromuscular blocking agents and the postsynaptic receptor occupation ratio. According to the simulations performed, the pharmacodynamic parameters determined: KB-apparent value of equilibrium constant of fazadinium — receptors exchange (mean ± SEM) 0.404+0.045 µmol/l, and the value of postsynaptic occupation ratio for 50% paralysis of 0.89±0.004 were in agreement with values reported in the literature for mammalian neuromuscular junctions in vitro. The apparent validity of the pharmacodynamic model and its value in simulating dose/effect relationships of non-depolarizing neuromuscular blocking agents are discussed and illustrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610063
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  • 55
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of bredinin in renal transplant patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 457-461 
    Details
    ISSN: 1432-1041
    Keywords: bredinin ; immunosupressive agent ; pharmacokinetics ; renal transplant patients ; renal function ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A pharmacokinetic study of bredinin, a new immunosupressive agent, was carried out in 28 renal transplant patients. Serum bredinin concentration-time curves were analyzed using a one-compartment open model with a first order absorption process. The peak serum bredinin level appeared 2.4 h after oral administration of bredinin 50–200 mg. The calculated mean peak serum level was 0.852 µg/ml/mg/kg, when the dose was adjusted to the body weight of the patient. In the dosage range used of 0.85–4.46 mg/kg, a linear relationship was observed between the dose and the peak serum bredinin level. The elimination rate of bredinin from serum was dependent on kidney function, and the elimination rate constant was well correlated with the endogenous creatinine clearance. No circadian rhythm was apparent in the elimination rate constant. The absorption rate of bredinin from the gastrointestinal (GI) tract was affected by GI diseases. The need for dosage adjustment based on the renal function of the transplant patient is suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609886
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  • 56
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 503-507 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; pharmacokinetics ; renal failure ; antiarrhythmic drug ; haemodialysis ; cirrhosis ; acetyldigoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3±4.8 h (±SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5±4.6 h, which was calculated to correspond to removal of 25±14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10–55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2±4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609893
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  • 57
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of prenalterol after single and multiple administration of controlled release tablets to patients with congestive heart failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 495-502 
    Details
    ISSN: 1432-1041
    Keywords: prenalterol ; pharmacokinetics ; food ; congestive heart failure ; plasma levels ; urinary excretion ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of prenalterol, a partial β-adrenoceptor agonist, has been studied in 12 patients with congestive heart failure, following single and repeated oral doses of 40 mg b.i.d. as controlled release tablets. A tracer dose of3H-labelled drug was given i.v. on 2 occasions to establish the variability of the pharmacokinetic parameters. Plasma levels and urinary excretion of prenalterol were measured after the oral and intravenous doses, and in addition, total radioactive metabolites were determined after the i.v. administration. Only small differences in the pharmacokinetics were observed when the i.v. tracer dose was given with the single oral dose or with the oral maintenance dose at steady state. The mean plasma elimination half-life was 2.4 h, the apparent volume of distribution 2.61/kg and the total body clearance about 800 ml/min. About 90% of the dose was excreted in urine, of which 30% was the parent drug. The remaining fraction comprised three metabolites, which were quantified by HPLC. Plasma levels of prenalterol close to steady state were obtained within 2 days and were maintained on a b.i.d. dosage regimen with controlled release tablets. The levels were independent of whether the tablets were taken fasting or with a standardized light meal. An average of 14% of the oral dose was recovered as prenalterol in urine after a single dose and 16% after a maintenance dose at steady state. Thus, about 45–55% of prenalterol reached the systemic circulation. The pharmacokinetic parameters in patients with congestive heart failure differed slightly from those in healthy subjects, but not sufficiently to require a change in the oral dosage regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609892
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    Pharmacokinetics of gentamicin in very low birth weight preterm infants (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 649-653 
    Details
    ISSN: 1432-1041
    Keywords: gentamicin ; preterm infants ; pharmacokinetics ; low birth weight ; dosage regimens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Low birth weight preterm infants with suspected infection were administered gentamicin intramuscularly every 18 h (2.5 mg/kg) or 24 h (3.0 mg/kg). For both dosage regimens plasma gentamicin levels were monitored during a dosage interval on three separate occasions over a 10 day period. Both regimens gave satisfactory plasma concentrations and there was no important statistically significant difference between the two. The body clearance of gentamicin correlated with gestational age (r=0.76, p〈0.01). The results indicate either regimen may be useful in the clinical situation but from a practical standpoint administration every 24 h may be easier to comply with then every 18 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542216
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  • 59
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    Electronic Resource
    Systemic availability of acetylsalicylic acid in normal men and women and its effect on in vitro platelet aggregability (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 679-682 
    Details
    ISSN: 1432-1041
    Keywords: acetylsalicylic acid ; salicylic acid ; platelets ; pharmacokinetics ; sex difference ; platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3±2.0% and 16.9±3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5±1.4 and 18.1±1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9±2.9 µg/ml in females and 22.5±2.7 µg/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5±5.1 µg/ml in females (p〈0.02) and to 29.5±3.8 µg/ml in males (p〈0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542222
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  • 60
    Electronic Resource
    Electronic Resource
    Aspirin pharmacokinetics in migraine. The effect of metoclopramide (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 777-785 
    Details
    ISSN: 1432-1041
    Keywords: aspirin ; migraine ; salicylic acid ; metoclopramide ; drug absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of aspirin (ASA) in acute migraine attacks, and the influence of metoclopramide on ASA disposition, were studied in 32 attacks in 30 patients. An intergroup comparison was made between normal volunteers, and the migraineurs, who were assigned at random to one of three treatment groups: a) oral ASA only (900 mg); b) 10 mg oral metoclopramide + oral ASA 900 mg; c) 10 mg i. m. metoclopramide + oral ASA 900 mg. Plasma ASA and SA levels were measured serially over 2 h, and the resultant data evaluated pharmacokinetically. Metoclopramide plasma levels were also determined over 2 h, and the results compared with a second group of normal volunteers. The rates of oral ASA absorption and elimination were unaffected by migraine. Mean absorption rate constants of 14.15±9.48 h−1 (normals), 7.91±3.42 h−1 (ASA only), 6.74±3.26 h−1 (ASA + oral metoclopramide) and 8.12±2.82 h−1 (ASA + i. m. metoclopramide) were calculated. Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1, and did not differ significantly between controls and migrainous patients. Values for absorption lag time, however, were higher in migraine patients treated with ASA alone than in any other group. The amount of ASA absorbed unhydrolysed was also lower in this group. SA levels appeared unaffected either by the migraine attack, or by metoclopramide administration, over the period of study. Metoclopramide plasma levels were significantly lower during migraine attacks, and the amount of drug absorbed up to 2 h from dosing was also reduced, as compared with non-migrainous subjects. It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites, probably as a result of gastric stasis, and may have decreased the amount of ASA absorbed. The prior administration of metoclopramide, either orally or intramuscularly, reduced the absorption lag time, and thus promoted the early absorption of ASA, probably by restoring alimentary tract motility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607087
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  • 61
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    Electronic Resource
    Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 819-823 
    Details
    ISSN: 1432-1041
    Keywords: chloramphenicol ; children ; pharmacokinetics ; oral dose ; absorption ; i.v. dose ; kwashiorkor ; marasmus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/min/kg). In consequence the mean half-life was prolonged (3.76 h versus 2.85 h) and this led to somewhat higher plasma levels in the kwashiorkor children. The influence of the pathophysiological changes offset one another so that plasma concentrations within the therapeutic range were obtained in children with kwashiorkor given recommended standard i.v. doses. The absorption of chloramphenicol after oral administration in severely malnourished children was erratic, which suggests that this route should be avoided in such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607094
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  • 62
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    Tizanidine — Initial pharmacokinetic studies in patients with spasticity (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 65-67 
    Details
    ISSN: 1432-1041
    Keywords: tizanidine ; pharmacokinetics ; spasticity ; multiple sclerosis ; haematological parameters ; electromyogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time-course of plasma concentrations of the antispasticity agent tizanidine were measured by a specific radioimmune-assay in six adults who had severe spasticity due to multiple sclerosis. The drug was given as a single oral 4 mg dose to each subject. The drug had a mean absorption half-life of 0.30±0.155 h following a mean lagtime of 0.361±0.118 h, and a mean terminal elimination half-life of 4.16±2.06 h. Only 2.65±0.82% of the dose was excreted unchanged in urine in 2 h. Calculated values of clearance and apparent volume of distribution were almost certainly overestimates as it seems probable that the orally-administered drug undergoes significant presystemic elimination (its bioavailability was not determined in the investigation here reported). Relief of spasticity, from the dosage used, was relatively slight and appeared greatest at the time of peak plasma levels of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544016
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  • 63
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    Electronic Resource
    Effect of ethanol intake on disopyramide elimination by healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 103-105 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; ethanol ; pharmacokinetics ; interaction ; metabolic clearance ; renal clearance ; diuresis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of ethanol intake on disopyramide elimination was examined in an open cross-over study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the urine (p〈0.05) as well as the relative metabolic clearance of disopyramide (p〈0.05). The renal clearance of disopyramide was increased by 19±16% (p〈0.05) in subjects in whom ethanol caused a diuresis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544024
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  • 64
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    Cimetidine disposition in patients with Laennec's cirrhosis during multiple dosing therapy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 223-229 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; alcoholic cirrhosis ; multiple dosing ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of cimetidine after oral and intravenous administration during multiple dosing was studied in 11 patients with Laennec's cirrhosis. The average metabolic clearance of cimetidine in these patients was 151/h, similar to values reported for normal subjects. However, in 4 subjects with plasma prothrombin times above normal, the metabolic clearance was significantly decreased and ranged between 4.3 and 13.01/h. The renal clearance of cimetidine was proportional to the creatinine clearance in all subjects, regardless of the severity of the liver disease. The clearance of cimetidine in patients with Laennec's cirrhosis, therefore, appears to be predictabable from creatinine clearance and prothrombin time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543795
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  • 65
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    CSF penetration and pharmacokinetics of midazolam (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 247-251 
    Details
    ISSN: 1432-1041
    Keywords: midazolam ; CSF penetration ; pharmacokinetics ; benzodiazepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The passage of midazolam, a new benzodiazepine derivative with highly water-soluble salts, into cerebrospinal fluid (CSF) was studied after a single oral dose of 15 mg (n=23), a single i.m. injection of 0.075 or 0.150 mg/kg (n=8), or a single i.v. dose of 0.075 mg/kg (n=26). Contrary to previous studies of diazepam and flunitrazepam, the rapid clinical effect of midazolam cannot be explained by rapid passage into human lumbar CSF. In only four cases following intravenous injection was there a measurable amount of drug in lumbar CSF (lower limit of assay sensitivity=2 ng/ml). After both oral (n=10) and intramuscular (n=8) administration, midazolam was rapidly absorbed, with attainment of the peak serum level after about 0.5 h. The pharmacokinetic parameters following i.v. injection of midazolam (n=6) explain its rapid but brief duration of action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543799
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  • 66
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    Erythromycin absorption in healthy volunteers from single and multiple doses of enteric-coated pellets and tablets (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 271-273 
    Details
    ISSN: 1432-1041
    Keywords: erythromycin ; tablets absorption ; enteric-coated pellets ; blood concentrations ; healthy volunteers ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The absorption of erythromycin from two different enteric-coated preparations was evaluated in three groups of healthy volunteers. After a single dose, taken after an overnight fast, absorption was significantly better from enteric-coated pellets than from tablets; both the mean peak serum concentration and the peak mean level were higher (p〈0.01) in all three groups, and the mean area under the serum concentration-time curve (AUC) was at least 65% larger. Eight out of 23 subjects showed no or only a very low serum concentration after the enteric-coated tablets. In a follow-up study, 250 mg doses were given 6-hourly for 3 days, and again the mean maximum serum concentration was significantly higher (p〈0.05) after the pellets. In conclusion, enteric-coated pellets led to more regular and predictable absorption of erythromycin than did coated tablets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543802
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  • 67
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    Electronic Resource
    Pharmacokinetics of pindolol in Kenyan Africans (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 425-426 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; Africans ; pharmacokinetics ; single dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pindolol was studied in 8 normal Africans following administration of a single oral 10 mg dose. The mean peak concentration was 30.2±5.0 ng·ml−1, the mean half-life (t1/2) of the elimination phase was 3.4±1.1 h, and the total body clearance was 628±13 ml·min−1. The apparent volume of distribution was 3.0±1.3 l·kg−1. The values are the same as those reported in Europeans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037959
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  • 68
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    Electronic Resource
    Chronic propranolol administration during pregnancy (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    Details
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542115
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  • 69
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    Electronic Resource
    Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 511-515 
    Details
    ISSN: 1432-1041
    Keywords: 5-aminosalicylic acid ; inflammatory bowel disease ; sulphasalazine disposition ; pharmacokinetics ; healthy volunteers ; urinary excretion ; biliary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (± SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10±0.07 and 0.50±0.20 µg/ml, respectively) and SZ (0.12±0.14 and 0.67±0.14 µg/ml, respectively). Urinary excretion of total AS (5-AS+AcAS), too, was similar (192±70 and 179±79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21±0.22 µg/ml; AcAS 0.83±0.40 µg/ml) and in 5 healthy volunteers (5-AS 0.28±0.14 µg/ml; AcAS 1.10±0.43 µg/ml). Urinary recovery of total AS averaged 20±6% (patients) and 27±10% (volunteers). The cross-over trial in 7 patients with a biliary T-tube revealed that after single doses of 5-AS 1 g and SZ 2 g between 0.01% and 0.75% could be recovered in collected bile (85–500 ml/day) as total AS (traces of free 5-AS, and acetylated and glucuronidated 5-AS), indicating some enterohepatic circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542120
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  • 70
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    Electronic Resource
    Pinacidil, a new vasodilator: Pharmacokinetics and pharmacodynamics of a new retarded release tablet in essential hypertension (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 557-561 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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    URL: http://dx.doi.org/10.1007/BF00542128
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  • 71
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    Penetration of lidocaine and its active desethylated metabolite into cerebrospinal fluid in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 639-641 
    Details
    ISSN: 1432-1041
    Keywords: Lidocaine ; CSF penetration ; monoethylglycinxylidide ; glycinxylidide ; pharmacokinetics ; serum protein binding ; membrane permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Penetration into lumbar cerebrospinal fluid (CSF) of lidocaine and its active desethylated metabolite, monoethylglycinxylidide (MEGX), has been studied in 10 neurological patients after a single subcutaneous injection of 2 mg/kg prior to lumbar puncture. An HPLC method was used to assay lidocaine, MEGX and glycinxylidide (GX) in serum and CSF. The serum protein unbound fraction of lidocaine was determined by equilibrium dialysis. The mean peak serum lidocaine concentration was found 25 minutes after injection, and the corresponding peak CSF level occurred after 70 min. A similar slow penetration of MEGX into CSF was observed, which indicates low membrane permeability for these two agents. No GX was found. The steadily increasing CSF lidocaine/serum total lidocaine ratio throughout the period of study up to 120 min and the higher level in CSF than the corresponding unbound fraction of the total serum lidocaine indicate that serum protein binding is not the sole determinant of the penetration of lidocaine into lumbar CSF. Rapid accumulation in brain tissue and diffusion back into cerebral extracellular fluid and to lumbar CSF may also occur. The apparent slow membrane penetration of lidocaine and its desethylated metabolite may be one reason for the difficulty of controlling lidocaine infusion rates according to therapeutic effectiveness and side-effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542352
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  • 72
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    Disposition and removal of metronidazole in patients undergoing haemodialysis (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 683-687 
    Details
    ISSN: 1432-1041
    Keywords: metronidazole ; haemodialysis ; renal disease ; pharmacokinetics ; metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodialysis clearance of metronidazole were investigated in four renal failure patients after a single 500 mg intravenous dose and in two renal failure patients on continuous treatment with metronidazole. During dialysis, the volume of distribution of metronidazole was 0.60±0.04 l/kg, total clearance was 196.0±60.6 ml/min and the elimination half-life had an harmonic mean of 2.14 h. Extraction across the dialyser was 51.5±7.8% and was limited to the distribution of drug in plasma water. Dialysis clearance was 125.0±32.7 ml/min, which represented 62±6% of total clearance and was 1.75 times the sum of the other clearance mechanisms. The hydroxy metabolite was extracted and cleared by the dialyser to the same degree as metronidazole itself. During the 4 h-dialysis 44.9±2.6% of the dose was removed by the dialyser in the four patients administered a single dose. Metronidazole is efficiently cleared and extensively removed by dialysis, and therefore dosage adjustments and alterations in the timing of dosage administration are essential in patients undergoing haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542359
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  • 73
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    Disposition kinetics of metronidazole in children (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 113-119 
    Details
    ISSN: 1432-1041
    Keywords: metronidazole ; trichomonas vaginitis ; children ; pharmacokinetics ; serum and saliva concentrations ; therapeutic dosage schedule ; anaerobic infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of metronidazole was studied in 20 paediatric patients aged 6 weeks and 4 to 14 years, who had trichomonal vaginitis or an anaerobic bacterial infection. The dosage of metronidazole was about 10 or 20 mg/kg b.i.d. orally. The serum concentrations found in children and the corresponding calculated kinetic parameters were similar to those in adults after intake of an equal, weight-related dose. Metronidazole shows rapid diffusion into the saliva with a concentration ratio of about 1.0. This can provide the basis for an efficient non-invasive method of drug monitoring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613937
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  • 74
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    Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613808
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  • 75
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    Electronic Resource
    Intravenous administration of enprofylline to asthmatic patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 323-327 
    Details
    ISSN: 1432-1041
    Keywords: enprofylline ; theophylline ; constant infusion ; bronchodilator effect ; adverse reactions ; pharmacokinetics ; asthmatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from pressessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, head-ache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610048
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  • 76
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    Electronic Resource
    Pharmacokinetics of diltiazem in severe renal failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 635-638 
    Details
    ISSN: 1432-1041
    Keywords: calcium antagonist ; diltiazem ; renal failure ; pharmacokinetics ; desacetyldiltiazem ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects of a single dose of diltiazem (Tildiem®), a calcium antagonist, were studied in 9 patients with severely impaired renal function (GFR between 0.03 and 0.87 ml/s/1.73 m2). Control measurements were made of inulin and PAH clearance, creatinine, blood pressure, heart rate and ECG. Following administration of diltiazem 120 mg, 7 blood samples were collected in the first 12 h and after 24 h, 32 h, 48 h; urine was collected for the first 12 h, 12–24 h and 24–48 h, and blood pressure, heart rate and ECG were recorded after 6 h. Diltiazem and its main metabolite, desacetyldiltiazem, had a pharmacokinetic profile similar to that in patients with normal renal function (peak plasma concentration, half-life and urinary excretion). Diltiazem is normally eliminated in the urine to a small extent, because it is metabolized, and this also applies to desacetyldiltiazem, which is probably further metabolized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542213
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  • 77
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    Electronic Resource
    Comparative pharmacokinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 655-660 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; chlorthalidone ; co-administration ; pharmacokinetics ; healthy subjects ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers. The pharmacokinetic profile of metoprolol 100 mg was not affected by pretreatment with or co-administration of chlorthalidone 25 mg twice daily. Similarly, the pre-dosing steady-state level of chlorthalidone during chronic treatment and its blood level profile after a single 25 mg dose were not affected by metoprolol. The bioavailabilities of the 2 drugs administered in combination were identical to those observed when each drug was administered alone. These studies demonstrate that there is no pharmacokinetic interaction between metoprolol and chlorthalidone when doses of 100 and 25 mg, respectively, are co-administered twice daily.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542217
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  • 78
    Electronic Resource
    Electronic Resource
    Steady state disposition of chloroquine in patients with rheumatoid disease (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 837-839 
    Details
    ISSN: 1432-1041
    Keywords: chloroquine ; chloroquine metabolites ; pharmacokinetics ; rheumatoid disease ; renal clearance ; dosage schedule ; total body clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state disposition of chloroquine and its major metabolites, monodesethyl and bidesethyl chloroquine, were determined in 6 patients on long-term treatment for rheumatic disease with 99–155 mg base/day. The total body clearance of chloroquine was 0.35 l/kg/h and that of its metabolites was much higher. The renal clearance was the same for all compounds measured, ≈0.1 l/kg/h. Currently recommended dosage schedules appear to be too high in certain cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607097
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  • 79
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    Electronic Resource
    Investigation for the mechanism of cadmium toxicity at cellular level (1983)
    Springer
    Archives of toxicology 52 (1983), S. 99-108 
    Details
    ISSN: 1432-0738
    Keywords: Cadmium ; Toxicology ; Electron microscopy ; Endothelium ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With quantitative techniques at electron microscopical level chromatin condensation and emptying of the interchromatin space have been established in the nuclei of the endothelial cells of small uterine vessels. The nuclear and cytoplasmic changes after cadmium administration show much similarity between endothelial cells of small uterine vessels and cultured liver parenchymal cells. Cytoplasmic changes in both cell types after cadmium administration are suggestive of a disturbance in ribosomal RNA synthesis as the main cause leading to ultimate cell lysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00354770
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  • 80
    Electronic Resource
    Electronic Resource
    Fenofibrate and human liver (1983)
    Springer
    Archives of toxicology 53 (1983), S. 151-163 
    Details
    ISSN: 1432-0738
    Keywords: Fenofibrate ; Human liver ; Electron microscopy ; Morphometry ; Peroxisomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rodents fenofibrate shares with other triglyceride-lowering agents the potential to increase the liver peroxisome population. It was therefore of interest to look for this effect in hyperlipoproteinemic patients receiving this drug. Light and electron microscopy of liver biopsies from a group of 10 patients treated with fenofibrate and from another group of 15 receiving diet only, show no morphological difference between both groups. In contrast with the rodent data the morphometric study reveals no significant changes in the number (fenofibrate group: 7.96 1010 cm−3; group receiving diet alone: 8.41 1010 peroxisomes/cm3 of liver tissue) or in the size (fenofibrate group: Diameter=0.53±0.07 μm — group receiving diet alone: 0.50±0.06) of peroxisomes. The difference between our results and those obtained consistently in rodents may be due to the relatively low dose in man and/or a species-dependant difference in enzyme content of liver peroxisomes, itself related to an apparent difference in the way in which lipids are handled.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302723
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  • 81
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    Electronic Resource
    Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031) (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 251-253 
    Details
    ISSN: 1432-1041
    Keywords: chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613827
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  • 82
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    Electronic Resource
    Effect of ranitidine on the steady state pharmacokinetics of diazepam (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 357-360 
    Details
    ISSN: 1432-1041
    Keywords: diazepam ; ranitidine ; pharmacokinetics ; hydroxycorticosteroids ; hepatic enzymes ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 6 healthy volunteers the steady state pharmacokinetics of diazepam (5 mg p.o. once daily) was investigated in a randomized cross-over study with and without concomitant doses of ranitidine (150 mg bid). Following the last dose of diazepam on Day 10 of each part of the study, the plasma concentrations of diazepam were monitored for one dosing interval plus the subsequent 2 days. In addition, urinary excretion of 6-β-hydroxycortisol and 17-hydroxycorticosteroids were measured, their ratio being taken as an indicator of hepatic enzyme activity. Coadministration of ranitidine significantly reduced (p〈0.03) the trough and steady state concentrations (mean ± SD) of diazepam (114±36 Vs 104±30 ng/ml and 170±55 Vs 125±36 ng/ml, respectively). Plasma protein binding of diazepam (98.5±0.3%) was not affected by ranitidine. The half-life of elimination of diazepam (42.5±13.5 h) did not change significantly but its apparent oral clearance (assuming complete absorption) was significantly increased (p〈0.005) by ranitidine, from 22.6±9.2 to 30.0±9.1 ml/min. Urinary excretion of 6β-OH-cortisol (p=0.029) and 17-OH-corticosteroids (p=0.041) were significantly elevated by ranitidine, but their ratio did not change. In addition, in 4 additional subjects the disposition of diazepam following a single intravenous dose of 0.1 mg/kg was not significantly altered by ranitidine. Thus, the lowered steady state concentration of diazepam is most likely due to diminished absorption caused by the concurrent administration of ranitidine. However, it may be more important clinically that, unlike cimetidine, ranitidine did not impair the hepatic elimination of diazepam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610055
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  • 83
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    Electronic Resource
    The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 387-390 
    Details
    ISSN: 1432-1041
    Keywords: valproic acid ; epilepsy ; uremia ; pharmacokinetics ; peritoneal dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 h after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610060
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  • 84
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    Electronic Resource
    Biological variability of multiple dose pharmacokinetics of netilmicin in man (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 399-406 
    Details
    ISSN: 1432-1041
    Keywords: netilmicin ; aminoglycoside antibiotics ; nephrotoxicity ; pharmacokinetics ; multiple dose ; i.m. route ; individual variability ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Intra- and interindividual variability in the serum kinetics and renal elimination of netilmicin was investigated in a controlled study in 6 healthy, male volunteers. The antibiotic was administered on 2 single days, separated by a 3 week interval. Netilmicin 2 mg/kg lean body mass was given i.m. twice (b.i.d.) and three times (t.i.d.) in a crossover design. 54 blood and 28 urine samples per volunteer were analysed by a radio-enzymatic assay. 24 h serum kinetics were best described by a two compartment open model with time-dependent serum clearance. The latter decreased intraindividually on both study days, from a mean of 82 to 68 ml/min (p〈0.05). A similar decrease was observed in the 12 h creatinine clearance. Because drug administration started in the morning, this finding reflects the physiological circadian rhythm in the glomerular filtration rate. The corresponding half-lives of netilmicin rose from 149 to 171 min. Striking intraindividual variation in absorption half-life was observed in all volunteers, ranging from less than 4 to more than 30 min. Comparison of the pharmacokinetic parameters derived from data of the first and second study, revealed a significant intraindividual reduction in the volume of distribution (mean decrease 13%) and in the serum clearance of netilmicin (−8%). Analysis of the serum data of the b.i.d. and t.i.d. dosing schedules showed no difference in the pharmacokinetic parameters; there was significantly higher urinary recovery with the t.i.d. (+9%) than with the b.i.d. schedules. After both days, the 24 h creatinine clearance decreased significantly, by more than 10%. A slight nephrotoxic effect, induced by a therapy for one day with netilmicin, can be deduced from these data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610062
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  • 85
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    Electronic Resource
    Steady-state kinetics and analgesic effect of oral morphine in cancer patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 537-542 
    Details
    ISSN: 1432-1041
    Keywords: morphine ; analgesic activity ; tablets solution ; pharmacokinetics ; bioavailability ; pain score ; dose-response relationship ; chronic pain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state kinetics of morphine given as tablets and solution were compared in 7 cancer patients with chronic pain. There was no accumulation of morphine (20–40 mg) when repeatedly administered every 4 to 6 h. The mean steady-state concentration of morphine during the dose interval varied between 5.9 and 68.4 ng/ml (20.7–240 nmol/l), and was linearly related to the daily dose of morphine. There were no significant differences between the tablets and the solution of morphine with regard to relative oral bioavailability or peak concentration. The time-to-maximum plasma concentrations was significantly longer for the tablets. The pain score profile, assessed by a visual analogue scale during a dose interval, showed a similar pattern after the two oral formulations of morphine. No significant linear relationship between the scores and the plasma concentrations of morphine was observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609900
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  • 86
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    Electronic Resource
    Influence of age on amikacin pharmacokinetics in patients without renal disease. Comparison with gentamicin and tobramycin (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 639-642 
    Details
    ISSN: 1432-1041
    Keywords: amikacin ; pharmacokinetics ; gram negative infection ; normal renal function ; gentamicin ; tobramycin ; interpatient variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of age on amikacin pharmacokinetics was examined in 87 patients with normal renal function. All patients had a gram negative infection, were febrile, weighed within 20% of their ideal body weight, did not receive penicillin antibiotics concurrently, had normal hematocrits and had a measured 24 h creatinine clearance greater than 80 ml/min/1.73 m2. 31 patients were 20–39 years old, 27 patients were between the ages of 40–59 years, and 29 patients were 60–79 years old. These patients were compared to patients in similar previous studies who received gentamicin or tobramycin. No significant differences in clearance, volume of distribution or half-life were found due to age within a single drug group (amikacin, gentamicin, or tobramycin) or among the 3 drug groups. However, a substantial amount of intersubject variability existed in the calculated pharmacokinetic parameters. Patients over 40 years old tended to be underdosed with amikacin and the other 2 aminoglycosides. The average amikacin dose needed to achieve the desired steady-state concentrations was 18.9 mg/kg/day. 52% of the amikacin patients required doses greater than the recommended maximum (15 mg/kg/day). Since aminoglycoside pharmacokinetics do not change as age increases, doses do not need to be arbitrarily changed in older patients with normal renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542214
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  • 87
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    Electronic Resource
    Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 419-424 
    Details
    ISSN: 1432-1041
    Keywords: dihydrocodeine ; pharmacokinetics ; acid metabolites ; radioimmunoassay ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6h–1.8h. The mean half-lives varied between 3.3h–4.5h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12–34%). The peak levels of the acidic metabolites occurred between 1.8h–2.0h after oral administration and 2.2h–2.5h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037958
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  • 88
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    Electronic Resource
    Pharmacokinetics of oral hydralazine in chronic heart failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 467-473 
    Details
    ISSN: 1432-1041
    Keywords: hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542113
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  • 89
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    Electronic Resource
    Pharmacokinetic aspects of guanfacine withdrawal syndrome in a hypertensive patient with chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 463-466 
    Details
    ISSN: 1432-1041
    Keywords: guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542112
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  • 90
    Electronic Resource
    Electronic Resource
    Lack of effect of astemizole on ethanol dynamics or kinetics (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 567-568 
    Details
    ISSN: 1432-1041
    Keywords: astemizole ; ethanol ; antihistamine ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of astemizole (10 mg daily for 7 days) on the kinetics and CNS depressant activity of ethanol have been examined in a double-blind cross-over study agonist placebo in 7 volunteers. There was no significant change in the elimination rate or AUC of the plasma ethanol concentration-time curve after astemizole. Central nervous system effects of ethanol as monitored by visual analogues of sedation, visual discrimination, pursuit rotor and reaction time were also unaffected by astemizole pretreatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542130
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  • 91
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    Electronic Resource
    Pharmacokinetics of betamethasone in healthy adults after intravenous administration (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 643-650 
    Details
    ISSN: 1432-1041
    Keywords: betamethasone ; pharmacokinetics ; cortisol ; high-performance liquid chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of betamethasone and its phosphate ester are described in 8 healthy adults after i. v. bolus injection of 10.6 mg betamethasone phosphate. Both compounds were measured by high-performance liquid chromatography with ultraviolet detection using sample handling methods which prevented hydrolysis of the ester in vitro. Betamethasone phosphate disappeared rapidly from plasma (mean half-life=4.7 min) as betamethasone levels rose. Betamethasone plasma levels reached a peak 10–36 min after administration of the phosphate before declining in a biexponential manner. The terminal slow disposition phase had a mean half-life of 6.5 h. Only about 5% of the dose was recovered from urine as betamethasone, indicating extensive extrarenal clearance of betamethasone. Protein binding and blood/plasma concentration ratio were also determined. In comparison with its stereoisomer, dexamethasone, betamethasone is also cleared mainly by metabolism but has a lower plasma clearance, is less plasma bound, has a higher blood/plasma concentration ratio, and a higher volume of distribution. Endogenous cortisol levels were measured in the subjects who received betamethasone phosphate and in a matched control group of 4 subjects who did not. Betamethasone abolished the normal episodic secretion of cortisol and rapidly reduced its plasma concentration to a basal level. Cortisol plasma levels were not restored at 24 h but had returned to normal by 48 h after dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542353
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  • 92
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    Electronic Resource
    Pharmacokinetics of oral mexiletine in patients with acute myocardial infarction (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 773-777 
    Details
    ISSN: 1432-1041
    Keywords: mexiletine ; myocardial infarction ; pharmacokinetics ; gastro-intestinal absorption ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To study the effects of acute myocardial infarction on its pharmacokinetics a single oral dose of 400 mg mexiletine HCl was administered to seven patients. The study was performed within 24 h of the onset of pain (Study I) and was repeated 10–14 days later, during the recovery phase (Study II). Mexiletine in plasma and urine was quantified by a GLC method. The peak plasma concentrations of mexiletine were 0.65±0.05 (SEM) µg/ml and 1.08±0.11 µg/ml (p〈0.05) in Studies I and II, respectively. The corresponding peak times were 4.68±2.04 h and 1.46±0.17 h (N.S.). The lag time averaged 0.48±0.08 h in Study I and 0.39±0.05 h in Study II (N.S.). The area under the plasma concentration-time curve remained unchanged. The elimination half-life was 15.03±0.61 h and 11.75±0.80 h (p〈0.01) in Studies I and II, respectively. The recovery of unchanged mexiletine in urine and its renal clearance was also the same in both studies. The plasma protein binding of mexiletine was similar in Studies I and II (61±2% and 63±3%; N.S.). Thus, the rate of gastrointestinal absorption of mexiletine was definitely slowed in the acute phase of myocardial infarction, whereas the extent of absorption was not altered. The prolongation of the elimination half-life of mexiletine in the acute phase of myocardial infarction is probably related to an increase in its volume of distribution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542518
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  • 93
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    Electronic Resource
    Pharmacokinetics of tocainide in patients with combined hepatic and renal dysfunction (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 787-790 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; cirrhosis ; pharmacokinetics ; renal dysfunction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of tocainide following an i.v. infusion of tocainide HCl 100 mg was studied in 6 patients with decompensated cirrhosis (ascites) and renal dysfunction. In one patient with active hepatic necrosis the terminal plasma half-life was 57.4, and in the others the half life ranged from 16.0 to 29.0 h. The increase in half-life was correlated with biochemical evidence of renal dysfunction, but not with individual tests of hepatic function. Non-renal clearance of tocainide was similar to values reported previously in healthy subjects and patients with acute myocardial infarction. The apparent volume of distribution of tocainide was increased and the pattern of distribution was abnormal in some patients, as plasma concentrations increased after an initial fall and the elevated concentrations then persisted for several hours. This abnormality appeared to be most marked in patients with the greatest degree of liver dysfunction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542521
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  • 94
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    Electronic Resource
    Age differences in effects on blood pressure, flicker fusion frequency, salivation and pharmacokinetics of single oral doses of dothiepin and amitriptyline (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 811-814 
    Details
    ISSN: 1432-1041
    Keywords: age difference ; antidepressants ; blood pressure ; flicker fusion frequency ; salivation ; pharmacokinetics ; dothiepin ; pharmacodynamics ; amitriptyline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood pressure, critical flicker fusion frequency (CFF), salivary flow rate and pharmacokinetics were compared in 7 young healthy volunteers (average age: 22.7 years) and in 7 elderly healthy volunteers (average age: 70.6 years) after single oral doses of the antidepressants dothiepin (DP) 25 mg and amitriptyline (AMP) 25 mg. Systolic blood pressure fell further and the reduction lasted longer in the elderly than in the young after both drugs. The decrease in CFF after AMP 25 mg, and the reduction in salivary flow rate after either DP 25 mg or AMP 25 mg were larger in the elderly than in the young. Plasma levels, T1/2 and Cl of both drugs in the elderly were also higher, longer and smaller, respectively, in the elderly. Clearance was found to be reduced in the elderly. More cautions dosage regimens of these drug should be considered for elderly patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542525
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  • 95
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diltiazem after intravenous and oral administration (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 349-352 
    Details
    ISSN: 1432-1041
    Keywords: diltiazem ; pharmacokinetics ; intravenous dose ; oral dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic profile of diltiazem, a novel calcium antagonist, was studied in 12 volunteers following oral (60 mg) and intravenous (15 mg) administration. After i.v. administration biphasic elimination was observed, with a distribution half-life of 0.3±0.2 h and an elimination half-life of 3.1±1.0 h; the apparent volume of distribution was 5.3±1.71/kg and the total clearance was 1.28±0.48 l/kg/h. After the oral dose the elimination phase had a half-life of 3.2±1.3 h. The absolute bioavailability of diltiazem ranged from 24 to 74% (mean 42±18%). The interindividual variation may be explained by a variable first pass effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610053
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  • 96
    Electronic Resource
    Electronic Resource
    Delayed elimination of triamterene and its active metabolite in chronic renal failure (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 453-456 
    Details
    ISSN: 1432-1041
    Keywords: triameteren ; renal failure ; hydroxytriamterene sulphate ; pharmacokinetics ; plasma protein binding ; urinary excretion ; renal tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of triamterene and its active phase II metabolite were studied in 32 patients with various degrees of impaired renal function; the creatinine clearances ranged from 135 to 10 ml/min. The area under the plasma concentration-time curves (AUC) for triamterene were not influenced by kidney function, but the AUCs for the effective metabolite OH-TA-ester were significantly elevated in renal failure, indicating accumulation of the metabolite. Urinary recovery of triamterene and its metabolite over a 48 h collection period was significantly reduced in renal failure. This is considered to be due to delayed urinary excretion, corresponding to reduced renal clearance. The renal clearance of the native drug exceeded that of the metabolite, because of their different protein binding, 55% for triamterene and 91% for the metabolite. The latter is eliminated almost exclusively via tubular secretion and extrarenal elimination is less important. Administration of this antikaliuretic is therefore considered hazardous in patients with impaired kidney function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609885
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  • 97
    Electronic Resource
    Electronic Resource
    Relationship between pharmacokinetic and pharmacodynamic behaviour of bufuralol and its metabolite Ro 3-7410 in hypertensive patients (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 479-484 
    Details
    ISSN: 1432-1041
    Keywords: bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609890
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  • 98
    Electronic Resource
    Electronic Resource
    Pharmacokinetics in man of a new antiarrhythmic drug, cibenzoline (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 509-515 
    Details
    ISSN: 1432-1041
    Keywords: cibenzoline ; pharmacokinetics ; bioavailability ; urinary excretion ; antiarrhythmic drug ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml · min−1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml · min−1 and 439 ml · min−1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609894
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  • 99
    Electronic Resource
    Electronic Resource
    The influence of duration of intravenous infusion of an acute dose on plasma concentrations of cimetidine (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 29-34 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; intravenous infusion ; pharmacokinetics ; peptic ulcer ; duration of infusion ; acute dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of cimetidine administered by bolus intravenous injection to critically ill patients has been associated with serious cardiac arrhythmias, due presumably to high initial plasma concentrations. The aim of this study was to determine the range of infusion times of a single 200 mg dose of cimetidine which would avoid high initial drug concentrations while maintaining a duration of effective concentrations no less than that resulting from bolus injection. Computer simulations of both maximum plasma cimetidine concentrations and duration of effective plasma cimetidine concentrations versus duration of infusion were based on mean pharmacokinetic date from 6 peptic ulcer patients who had received cimetidine 200 mg i.v. over 5 min. The simulations indicated that to reduce maximum plasma cimetidine concentrations by at least 50%, while maintaining the duration of effective plasma concentrations, the infusion time should be at least 30 min and no longer than 4.5 h. The validity of the simulations was subsequently tested in 4 of the patients, who received cimetidine 200 mg i.v. over 30 min. The mean maximum plasma concentration for the 30 min infusion (4.57±0.53 µg/ml) was, as predicted, approximately half that corresponding to bolus administration in these patients (8.97±1.96 µg/ml). Moreover, the duration of effective concentrations for the infusion (1.43±0.28 h) was significantly greater than that for the 5 min infusion (1.21±0.31 h). We suggest that where an acute intravenous dose of cimetidine (200 mg) is indicated, it should be administered over at least 30 min rather than as a bolus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544010
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  • 100
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketanserin in man (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 73-76 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; pharmacokinetics ; protein binding ; excretion ; oral dosing ; i.v. injection ; first-pass effect ; antihypertensive drug ; serotonin antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Kinetic data for the new antihypertensive agent ketanserin were determined in six healthy subjects after single oral (40 mg) or intravenous (0.15 mg/kg) doses. Plasma protein binding was 94.0±1.8% (mean±SD). Cumulative urinary excretion of unchanged drug was less than 4% within 48 h following the single dose. The maximal plasma level (cmax) of 193±98.2 µg/l occured within 0.5 to 4.0 h after oral intake. The ketanserin plasma level declined biexponentially after oral administration, and triexponentially over the 36 h following intravenous injection. The terminal elimination half-life (term. t1/2) averaged 12.4±2.9 h and 12.8±4.8 h following oral and intravenous application, respectively. Total plasma clearance was 410±62.0 (i.v.) and 829±228 ml/min (p.o.) and the intravenous blood clearance averaged 602±91 ml/min, which indicates partly flowdependent hepatic elimination. A substantial first-pass effect led to a bioavailability of about 50% (range: 27–69%). Hepatic clearance of ketanserin followed the non-restrictive pattern. No change in blood pressure or heart rate was observed following ketanserin administration to normal volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544018
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