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  • Engineering General  (1,230)
  • pharmacokinetics  (814)
  • Magnetic resonance imaging  (749)
  • 11
    Electronic Resource
    Electronic Resource
    Renal excretion and pharmacokinetics of methotrexate and 7-hydroxy-methotrexate following a 24-h high dose infusion of methotrexate in children (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 231-238 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; hydroxymethotrexate ; lymphoid malignancy ; renal excretion ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In children with lymphoid malignancies 18 courses of methotrexate (18–200 mg/kg) administered as a 24-h infusion were monitored. Plasma concentrations and renal excretion rates of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) were determined. A low correlation was found between the administered dose of MTX and the body exposure to MTX or 7-OHMTX. Although 84% of the MTX eventually recovered from the urine was excreted during the 24 h of the infusion, the renal clearance of MTX was markedly lower during the time of the infusion than after it. There were courses with a low and others with a high renal clearance of MTX during the infusion, despite the same urine flow. A low MTX renal clearance was correlated with a high body exposure to MTX. As the same variations were also seen in the same patient during successive courses, pharmacokinetical characterization of patients appears questionable. The renal clearance of 7-OHMTX was significantly lower than the renal clearance of MTX, and the body exposure to 7-OHMTX ranged from 2–40% of the MTX body exposure. Treatment courses with a low or a high body exposure to 7-OHMTX were not associated with different urinary recoveries of the metabolite. Differences in MTX hydroxylation could not be substantiated. Because the concentration of 7-OHMTX is high soon after the end of an infusion, a specific method of MTX determination should be chosen for controlling treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614310
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and tolerance of a new penem antibiotic, FCE 22101, in healthy volunteers after a single intravenous dose (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 633-635 
    Details
    ISSN: 1432-1041
    Keywords: FCE 22101 ; penem antibiotic ; pharmacokinetics ; single dose ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The clinical tolerance and pharmacokinetics of FCE 22101 (sodium (5R, 6S)-6-[(1R)-hydroxyethyl]-2-carbamoyloxymethyl-2-penem-3-carboxylate), a new penem antibiotic, have been studied after giving a single i.v. dose of 4 mg·kg−1 to ten healthy male volunteers. The pharmacokinetics was estimated according to a two-compartment open model. The peak plasma concentration (Cmax) was 15.5 (1.08) µg·ml−1, mean (SEM). FCE 22101 was rapidly cleared from the systemic circulation [ $$t_{1/2\lambda _z } $$ =44.2 (4.2) min; CL=7.21 (0.47) ml·kg−1·min−1]. The mean apparent volume of distribution at steady-state was 246 (16.9) ml·kg−1. The mean residence time relative to the 10 min infusion was 39.4 (1.5)min. Urinary recovery of FCE 22101 showed wide inter-subject variation, ranging from 10.2 to 53.6% of the dose. No subject complained of adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637750
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  • 13
    Electronic Resource
    Electronic Resource
    The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 163-168 
    Details
    ISSN: 1432-1041
    Keywords: Tolbutamide ; diabetes mellitus ; non-insulin dependent ; pharmacokinetics ; pharmacodynamics ; glucose ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is uncertain how the hypoglycaemic effect of sulphonylureas varies with drug concentration in patients with non-insulin-dependent diabetes mellitus. The interrelationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group). In the observational group, tolbutamide concentration depended significantly on the daily dose, time from dose to sampling, body weight, and age. Blood glucose and insulin concentration were related, but were independent of tolbutamide concentration. In the experimental group, peak, but not pre-dose, tolbutamide concentration, depended on dose and on body mass index. Fasting and maximum post-prandial blood glucose concentration were positively correlated with maximum tolbutamide concentration, probably because tolbutamide dosage was highest in those with the poorest response. In the subset with a fasting blood glucose concentration of less than 8 mmol·l−1, neither glucose nor insulin concentrations depended significantly on tolbutamide concentrations. Tolbutamide concentration does not directly determine hypoglycaemic response in outpatients, and therapeutic monitoring of drug concentrations would not improve the management of such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280071
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  • 14
    Electronic Resource
    Electronic Resource
    Sequential administration of temozolomide and fotemustine: Depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours (1999)
    Springer
    Annals of oncology 10 (1999), S. 831-838 
    Details
    ISSN: 1569-8041
    Keywords: melanoma ; pharmacodynamics ; pharmacokinetics ; temozolomide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008304032421
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  • 15
    Electronic Resource
    Electronic Resource
    Carboplatin and cisplatin pharmacokinetics after intrapleural combination treatment in patients with malignant pleural effusion (1997)
    Springer
    Annals of oncology 8 (1997), S. 385-391 
    Details
    ISSN: 1569-8041
    Keywords: carboplatin ; cisplatin ; intrapleural combination ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Cisplatin (DDP) and carboplatin (CBDCA) are two of the mosteffective drugs in a locoregional approach. Since simultaneous combinedtreatment with intrapleural DDP and CBDCA has not been reported in humans, weinvestigated its use in patients with malignant effusions, focusing onpharmacokinetics. Patients and methods: The pharmacokinetics of DDP and CBDCA were studiedin 10 patients with malignant pleural effusion treated intrapleurally with acombination of DDP (60 mg/m2) and CBDCA (270mg/m2) and in additional patients who received the same dosesof drugs administered intravenously as single agents or in combination.Platinum (Pt) species originating from DDP (metabolites plus unchanged DDP)and intact CBDCA in plasma and pleural fluid ultrafiltrates were measured bymeans of high performance liquid chromatography and atomic absorptionspectrometry. Results: Both in the plasma and pleural fluid, the total levels of free Ptrepresented the additive result of the individual concentrations of CBDCA andPt-species derived from DDP. After intrapleural combination, highpleural-plasma ratios of the peak concentrations and AUCs were observed bothfor CBDCA and DDP-derived Pt species, highlighting a distinct localpharmacological advantage. However, the Pt species originating from DDP wereabsorbed more rapidly from the pleural cavity than CBDCA (Ka= 86 × 10-3 vs. 37 ×10-3 min-1, P 〈 0.05).Intrapleural combination of CBDCA and DDP produced therapeutic plasma levelsof reactive (free) DDP species and increased the extent of their residencetime (MRT) compared with single intravenous DDP treatment [peak concentration:1.1 ± 0.1 (SD) vs. 1.6 ± 0.2 µg/ml; MRT: 5.2 ± 1.9vs. 0.5 ± 0.06 h]. Furthermore, the plasma AUC of free CBDCA afterintrapleural combined treatment (2.1 ± 0.5 mg/ml × min) wassimilar to that after intravenous administration of CBDCA alone (2.1 ±0.2 mg/ml × min). The intrapleural treatment was well tolerated by allpatients. Toxicity consisted of mild nausea and vomiting (grade 1–2according to the WHO scale) in four patients. Myelosuppression (grade1–2) was remarkable only in two heavily pretreated patients. No evidenceof recurrence of the pleural effusion was observed in six patients (completeresponse), while an asymptomatic minimal fluid reaccumulation not requiringdrainage (partial response) was observed in four patients. Conclusions: The pharmacologic results seem to exclude a pharmacokineticinteraction between CBDCA and DDP and suggest that a dose of CBDCA 2-foldhigher than that used in this study associated intrapleurally with 60mg/m2 DDP could induce an acceptable and predictablemyelosuppresion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008203100410
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  • 16
    Electronic Resource
    Electronic Resource
    An unusual presentation of congenital infantile myofibromatosis arising from the interspinous ligament (1998)
    Springer
    Pediatric surgery international 14 (1998), S. 138-139 
    Details
    ISSN: 1437-9813
    Keywords: Key words Myofibromatosis ; Fibromatosis ; Soft-tissue tumor ; Interspinous ligament ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The authors describe an extremely rare presentation of congenital infantile myofibromatosis. A full-term newborn boy presented with a thumb-sized subcutaneous mass on the mid-spinal line between the 2nd and 3rd lumbar spinous processes. A solid tumor arising from the interspinous ligament was resected. Microscopic and immunohistochemical studies revealed myofibromatosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050463
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  • 17
    Electronic Resource
    Electronic Resource
    The determination of dimethindene in human serum by enzyme-linked immunosorbent assay (EIA)
    Amsterdam : Elsevier
    Journal of Pharmaceutical and Biomedical Analysis 11 (1993), S. 619-623 
    Details
    ISSN: 0731-7085
    Keywords: EIA ; ELISA ; Fenistil. ; dimethindene ; dimethindene maleate ; pharmacokinetics
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0731-7085(93)80014-R
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  • 18
    Electronic Resource
    Electronic Resource
    Leukoencephalopathy with swelling in children and adolescents: MRI patterns and differential diagnosis (1995)
    Springer
    Neuroradiology 37 (1995), S. 679-686 
    Details
    ISSN: 1432-1920
    Keywords: Leukoencephalopathy ; White matter swelling ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In children, several neurological disorders are characterised by spongiform leukoencephalopathy. MRI of the brain typically shows white matter swelling, but does not enable differentiation of the various underlying disorders. The aim of this article is optimisation of the diagnostic value of MRI in leukoencephalopathy accompanied by swelling. MRI-based inclusion criteria were met by 20 patients in our database. The images were analysed using a detailed scoring list. In 13 of the 20 patients the clinical diagnosis was known (11 definite and 2 probable diagnoses). Characteristic MRI abnormalities could be defined in these patients. Of the 7 patients without a diagnosis, 5 had identical MRI abnormalities: difuse hemisphere swelling and typical cysts in frontoparietal subcortical white matter and the tips of the temporal lobes. The clinical picture was also similar in these patients, suggesting a similar disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00593394
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  • 19
    Electronic Resource
    Electronic Resource
    Leukoencephalopathy with swelling in children and adolescents: MRI patterns and differential diagnosis (1995)
    Springer
    Neuroradiology 37 (1995), S. 679-686 
    Details
    ISSN: 1432-1920
    Keywords: Key words Leukoencephalopathy ; White matter swelling ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In children, several neurological disorders are characterised by spongiform leukoencephalopathy. MRI of the brain typically shows white matter swelling, but does not enable differentiation of the various underlying disorders. The aim of this article is optimisation of the diagnostic value of MRI in leukoencephalopathy accompanied by swelling. MRI-based inclusion criteria were met by 20 patients in our database. The images were analysed using a detailed scoring list. In 13 of the 20 patients the clinical diagnosis was known (11 definite and 2 probable diagnoses). Characteristic MRI abnormalities could be defined in these patients. Of the 7 patients without a diagnosis, 5 had identical MRI abnormalities: diffuse hemisphere swelling and typical cysts in frontoparietal subcortical white matter and the tips of the temporal lobes. The clinical picture was also similar in these patients, suggesting a similar disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050179
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  • 20
    Electronic Resource
    Electronic Resource
    MRI of intracranial toxoplasmosis after bone marrow transplantation (2000)
    Springer
    Neuroradiology 42 (2000), S. 14-18 
    Details
    ISSN: 1432-1920
    Keywords: Key words Bone marrow, transplantation ; Toxoplasmosis, cerebral ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002340050003
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