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  • 2020-2022
  • 1990-1994  (2,334)
  • 1985-1989
  • 1992  (2,334)
  • Life and Medical Sciences  (2,215)
  • Genetics  (223)
  • pharmacokinetics
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  • 2020-2022
  • 1990-1994  (2,334)
  • 1985-1989
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  • 1
    Electronic Resource
    Electronic Resource
    The genetic basis of Ro and La antibody formation in systemic lupus erythematosus (1992)
    Springer
    Rheumatology international 11 (1992), S. 243-249 
    Details
    ISSN: 1437-160X
    Keywords: Systemic lupus erythematosus ; Ro and La antibodies ; Multicenter study ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies against Ro and La, including recombinant La and recombinant 60 kD-Ro, were determined by counter immunoelectrophoresis and ELISA in over 300 central European systemic lupus erythematosus (SLE) patients. The presence of both Ro and La antibodies was strongly associated with the MHC haplotype B8-C4AQ0-DR3-DQ2, the association being stronges for DR3. After exclusion of all B8-DR3 positive patients only DR3 positive patients still showed an increased incidence of Ro and La antibodies, suggesting DR3 as the primary association factor. High titers of La antibody, but not of 60 kD-Ro antibody, were also significantly associated with the presence of DR3. Other DR and DQ antigens or heterozygous DQ combinations were not significantly associated with Ro and La antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00301501
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  • 2
    Electronic Resource
    Electronic Resource
    MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus (1992)
    Springer
    Rheumatology international 12 (1992), S. 169-173 
    Details
    ISSN: 1437-160X
    Keywords: Systemic lupus erythematosus ; Genetics ; Ro and La antibodies ; Recombinant autoantigens ; MHC ; Multicenter study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302148
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  • 3
    Electronic Resource
    Electronic Resource
    L-Tyrosine-3-hydroxylase regulation in the brain: genetic aspects (1992)
    Springer
    Amino acids 3 (1992), S. 229-234 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; Tyrosine hydroxylase ; Brain ; Genetics ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary L-tyrosine-3-hydroxylase (TH) is the first and rate limiting enzyme in the biosynthetic pathway of catecholamine neurotransmitters (dopamine, noradrenaline, adrenaline). Implication of dopamine (DA) in various psychopathological phenomena, such as schizophrenia, has considerably contributed to the intensity of investigation of basic biochemical regulation of TH by activation and induction. Here we consider a third, constitutional (genotypic) aspect of regulation and present evidence that differences in mesencephalic (TH/SN), striatal (TH/CS), and hypothalamic (TH/HT) TH activity between virtually isogeneic strains of mice can be explained by segregating genetic factors. Biometrical genetic analysis of progenitor strains and their crosses indicated significant additive gene effects for TH/SN, TH/CS, and TH/HT, whereas dominance effects were statistically non-significant. A monogenic model of inheritance for TH/SN and TH/CS could not be rejected, while more than one gene was indicated for TH/HT. Significant positive phenotypic correlations were found in genetically segregating populations among mesencephalic, striatal and hypothalamic TH activities. This would suggest that some common genetic factors (or linked genes) are involved in the genetic variation of all three traits. A genetic selection experiment to elucidate the cellular and biochemical mechanisms underlying these variations is in progress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00805997
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  • 4
    Electronic Resource
    Electronic Resource
    Apolipoprotein genes and atherosclerosis (1992)
    Springer
    Journal of molecular medicine 70 (1992), S. 377-384 
    Details
    ISSN: 1432-1440
    Keywords: Genetics ; Apolipoproteins ; Lipoproteins ; Atherosclerosis ; Transgenic animals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to elucidate the genetic abnormalities underlying lipoprotein disorders associated with coronary heart disease susceptibility, researchers have looked for candidate genes. The studies have focused particularly on the lipoprotein transport genes. Relatively common as well as rare mutations have already been identified in several of these genes. In addition, further metabolic and genetic studies indicate that some of these loci harbor significant, but as yet undefined, genetic variation. In the next few years, it is not unreasonable to expect that all or most of the significant mutations at these loci will be catalogued. It is too early to know whether this will be sufficient to explain the genetic basis of altered lipoprotein levels or whether new loci will need to be investigated. Additional candidate gene loci might be those coding for genes involved in intracellular cholesterol metabolism, cholesterol absorption, or insulin resistance. New loci may also be revealed by the technique of reverse genetics. A more complete understanding of the genetics of atherosclerosis susceptibility will probably also entail the identification of variants at genetic loci that control both the reaction of the blood vessel wall to atherogenic lipoproteins and the thrombosis system. Investigation of the genetic basis of coronary heart disease susceptibility remains a worthwhile and lively field, with important clinical and public health ramifications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235516
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  • 5
    Electronic Resource
    Electronic Resource
    Identifying sex differences in reading disability (1992)
    Springer
    Reading and writing 4 (1992), S. 307-326 
    Details
    ISSN: 1573-0905
    Keywords: Genetics ; Reading disability ; Sex differences ; Twins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Education
    Notes: Abstract The issue of sex differences in reading disability has been of recent interest in relation to sex ratios in families with reading disabled children and to possible sex biases in referred populations. Data from a study of 570 twins are used to develop alternative definitions of reading disability that vary in the manner to which sex effects are taken into account. These definitions include discrepancies between reading quotients and IQ, the use of the regression of reading onto IQ and chronological age/reading age differences. In each case the reading and spelling disability was defined either separately for the sexes or based upon the data for the sexes combined and with and without an IQ〉90 exclusion criterion. The consequences of using the alternative definitions for prevalence, sex ratio and heritability are examined. The results demonstrate that the characteristics of reading disabled children vary with the way disability is defined. The excess of males seems to be a robust finding. Definitions that take into account differences in mean score for males and females reduce but do not eradicate the sex ratio. From the genetic analysis, there is no support for the suggestion that the genetic effect on reading is greater for females than males. It is concluded that the use of regression based procedures for identifying reading disability is desirable but that at present there is insufficient evidence to justify the adoption of separate regression procedures for the two sexes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01027711
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  • 6
    Electronic Resource
    Electronic Resource
    Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a welsh type 2 (non-insulin-dependent) diabetic population (1992)
    Springer
    Diabetologia 35 (1992), S. 486-489 
    Details
    ISSN: 1432-0428
    Keywords: Genetics ; Type 2 (non-insulin-dependent) ; diabetes mellitus ; insulin receptor ; glucose transporters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4383 variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of this mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects. The genotypic frequencies (homozygous wild-type and heterzygous polymorphic (poly) sequences) were not significantly different between diabetic and control subjects (Type 2 diabetic subjects: wild-type/wild-type 40%, wild-type/poly 46%, poly/poly 14%; Control subjects: wild-type/wild-type 37%0, wild-type/poly 45 %, poly/poly 18 %;p 〉 0.05). In conclusion, in a British Caucasian population the examined insulin receptor tyrosine kinase domain mutations are uncommon. Also the GLUT 4 locus does not appear to be strongly associated with Type 2 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02342449
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of rufloxacin in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 101-105 
    Details
    ISSN: 1432-1041
    Keywords: Rufloxacin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 μg · h · ml−1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p. o. was 715 μg · h · ml −1 in fasting subjects and 614 μg · h · ml−1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30–40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33–36 h and 50–80 h, respectively).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314928
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of meropenem in subjects with renal insufficiency (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 535-538 
    Details
    ISSN: 1432-1041
    Keywords: Meropenem ; Carbapenem ; pharmacokinetics ; uraemia ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 μg·ml−1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314864
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of mefloquine in the presence of primaquine (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 559-560 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314870
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of diphemanil methylsulphate in healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 689-691 
    Details
    ISSN: 1432-1041
    Keywords: Diphemanil methylsulphate ; pharmacokinetics ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic parameters of oral diphemanil methylsulphate have been evaluated in six healthy male volunteers. Absorption of the drug was slow (tmax=2 to 4 h), the mean half-life was 8.35 h, and the amount of the drug recovered in urine within 48 h ranged from 0.6 to 7.4% of the administered dose. The results suggest low bioavailability, assuming that the drug is poorly metabolized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265939
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  • 11
    Electronic Resource
    Electronic Resource
    Dose proportionality study of loperamide following oral administration of loperamide oxide (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 693-694 
    Details
    ISSN: 1432-1041
    Keywords: Loperamide ; loperamide oxide ; diarrhoea ; pharmacokinetics ; dose-proportionality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of loperamide, after oral administration of increasing doses (1 to 16 mg) of loperamide oxide, has been investigated in 10 healthy male volunteers, using a randomised cross-over design. Comparison of the maximum plasma loperamide concentration and AUC demonstrated that the bioavailability of loperamide was proportional to the dose of loperamide oxide administered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265940
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  • 12
    Electronic Resource
    Electronic Resource
    Evaluation of the accuracy of a pharmacokinetically-based patient-controlled analgesia system (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 67-75 
    Details
    ISSN: 1432-1041
    Keywords: Morphine ; Patient-controlled analgesia ; opioids ; pharmacokinetics ; bolus-elimination-transfer ; computer-assisted continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Bone marrow transplant patients having severe, prolonged oral mucositis pain (expected to last for one to three weeks) used a computer-controlled infusion system to self-administer morphine for pain control. Individual patient pharmacokinetic information, derived from a pretreatment bolus morphine dose, was used in a new bolus-elimination transfer algorithm to produce rapid adjustments of steady plasma morphine concentrations when the patient requested more or less drug. We evaluated the performance characteristics (bias and precision) of this pharmacokinetically based patient-controlled analgesic infusion system (PKPCA) in a group of 15 cancer patients over six to 14 days. Although we found a three- to fivefold pharmaco-kinetic variability in the tailoring morphine dose data, the PKPCA system was free of systematic bias (insignificant overall prediction error) during the patient-controlled infusions in this study population. The absolute prediction error was 19.9% for the group on the first study day and 25.6% over the entire study period (aggregate results; 6–14 days of continuous use). Two-thirds of the patients exhibited no bias throughout the study period, and individual bias in the others was symmetrically distributed (three patients with underpredictions and two overpredicted). Magnitude of prediction error during the patient-controlled morphine infusions was not related to the magnitude of pharmacokinetic deviation of individual subjects from group parameters. Our results indicate that this PKPCA system provides accurate control of plasma morphine concentration when used by patients to self-administer opioid for prolonged pain relief continuously over 1 to 2 weeks. Use of individual pharmacokinetic information, instead of population parameters, may account for superior performance characteristic of this computer-assisted continuous drug infusion system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02280757
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  • 13
    Electronic Resource
    Electronic Resource
    Steady state pharmacokinetic profile of indomethacin in elderly patients and young volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: Indomethacin ; steady-state ; pharmacokinetics ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state pharmacokinetic profile of indomethacin was examined in twelve healthy volunteers (4 m, 8 f; 20–34 y) and in 12 elderly subjects (7 m, 5 f; 70–88 y). Two formulations of indomethacin were examined, providing duplicate data for each subject group. The subjects received each formulation of indomethacin (25 mg tid) for 6 days in a single blind crossover fashion. On day 7, after an overnight fast, a final 25 mg dose of indomethacin was given and plasma concentrations measured over the following 12 h. Kinetic parameters Cpmin, tmx and AUC (0–12 h) were determined. There were no differences in the pharmacokinetic parameters between young and elderly subjects or between data for the two formulations of indomethacin. AUC values (μg · ml−1 · h), for example, for the two formulations in the young subjects were 5.85 and 6.85 while the values for the elderly subjects were 6.55 and 6.50 respectively. When each treatment period was considered independently there was a significant difference between young and elderly subjects with regard to compliance. The rates of non compliance (over and under compliance) using a capsule count technique were, however, low with a mean maximum value of 5.8% being recorded for the elderly subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02280758
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  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and dialysability of isradipine in chronic haemodialysis patients (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 231-233 
    Details
    ISSN: 1432-1041
    Keywords: Isradipine ; Haemodialysis ; pharmacokinetics ; dialysability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed. The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml−1, 1.4 h, 23.8 ng·h·ml−1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min−1). The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278492
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  • 15
    Electronic Resource
    Electronic Resource
    Disposition of quinine in plasma, red blood cells and saliva after oral and intravenous administration to healthy adult Africans (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 171-174 
    Details
    ISSN: 1432-1041
    Keywords: Quinine ; Malaria ; pharmacokinetics ; red blood cells ; plasma ; saliva ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quinine has been studied in ten healthy adult Africans after intravenous infusion and oral ingestion of a 500 mg dose. Blood and saliva samples were collected over 48 h and quinine in plasma, red cells and saliva was determined by HPLC. Quinine was rapidly and almost completely absorbed after an oral dose, with absorption half-life of 0.53 h, a tmax of 1–3 h and a bioavailability of 88%. Analysis of the i. v. data gave an apparent volume of distribution of 3.6 1·kg−1 and a plasma clearance of 0.19 l·kg−1·h−1. The concentration-time curves for plasma, red cells and saliva had declining phases were approximately parallel, giving a similar half-life that in all three media. The half-lives after the i. v. infusion also did not different from those after oral administration. The dose was well tolerated by both methods of administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278479
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  • 16
    Electronic Resource
    Electronic Resource
    Binding of a metabolite of triflusal (2-hydroxy-4-trifluoromethylbenzoic acid) to serum proteins in rat and man (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 175-179 
    Details
    ISSN: 1432-1041
    Keywords: 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) ; Triflusal ; triflusal metabolite (HTB) ; pharmacokinetics ; protein binding ; ultrafiltration ; binding constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet anti-aggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg·kg−1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K=intrinsic affinity constant, n=number of binding sites) were K1=1.4×105 l·mol−1, n1=1.23, and K2=4.1×103 l·mol−1 and n2=3.77. The mean plasma concentration in rats after oral administration was 185 (37) μg·ml−1 (protein-free HTB: 2.44 (0.77)%). The binding constants in human plasma were K1=4.7×105 l·mol−1, n1=1.93, K2=4.3 l·mol−1 and n2=4.28. The plasma HTB concentration in man (n=8) was 35 μg·ml−1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 μg·ml−1 (Cmax·ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 μg·ml−1 (Cmax·ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose. HTB had high affinity for plasma albumin, which was not saturable after therapeutic doses. It showed linear elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278480
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  • 17
    Electronic Resource
    Electronic Resource
    Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 181-185 
    Details
    ISSN: 1432-1041
    Keywords: Glycerol ; brain oedema ; serum ; cerebrospinal fluid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution IV over 4 h, serum and CSF were repeatedly sampled during and after the infusion and glycerol was measured enzymatically. The highest serum glycerol level of 191–923 mg/l was observed at the end of the infusion. The maximum CSF glycerol of 18.7–110.8 mg/l was attained 0–1 h after the end of the infusion. Elimination both from serum and CSF approximated a single-exponential decay; the elimination half-life from serum was 0.29–0.56 h compared to 1.03–3.68 h from CSF. In six of the seven cases there was a temporary reversal of the serum/CSF concentration gradient during glycerol elimination. The ratios of the AUCs of CSF and serum, which describe the overall penetration of glycerol into CSF, ranged from 0.09–0.31. In conclusion, the serum level of glycerol produced by giving 50 g IV glycerol over 4 h may not be sufficiently high reliably dehydrate to brain tissue in many patients, and the slow elimination of glycerol from the CSF may be related to the so-called rebound phenomenon.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278481
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  • 18
    Electronic Resource
    Electronic Resource
    Formation and excretion of dipyrone metabolites in man (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 187-191 
    Details
    ISSN: 1432-1041
    Keywords: Dipyrone ; Acetylation phenotype ; metabolism ; pharmacokinetics ; urinary excretion ; metabolite clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The formation and urinary excretion of the dipyrone metabolites, methylaminoantipyrine (MAA), aminoantipyrine (AA), formylaminoantipyrine (FAA) and acetylaminoantipyrine (AAA) were determined following administration of a single oral 1.0 g dose of dipyrone to 12 healthy volunteers. The AAA/AA plasma ratio showed that 3 subjects were slow and 9 were rapid acetylators. Pharmacokinetic parameters were determined separately for each group. A good correlation was found between the plasma and urine AAA/AA ratios. The renal clearance of the four metabolites was similar for both phenotypes. A significant difference in the rate of formation of dipyrone metabolites was found for AA, 0.25 (slow) vs 0.1 ml·min−1·kg−1 (rapid), and for AAA 0.75 (slow) vs 7.53 ml·min−1·kg−1 (rapid). There were comparable differences between slow and rapid acetylators in the AUC and the urinary excretion extrapolated to infinity for AA and AAA. The present results show that the kinetics of dipyrone metabolites in plasma and urine can provide a useful measure of the activity of the enzymes involved in their production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278482
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  • 19
    Electronic Resource
    Electronic Resource
    Effect of salbutamol on digoxin pharmacokinetics (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 197-201 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; Salbutamol ; serum ; skeletal muscle digoxin ; pharmacokinetics ; drug interaction ; serum potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A single dose of the β2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a β2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 μg·kg−1·h−1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i. v. injection of digoxin 15 μg·kg−1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0–6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium. The results support the hypothesis that the salbutamol-induced decrease in serum digoxin is caused by increased distribution of digoxin to skeletal muscle (and possibly other tissues), and that this may be secondary to a β2-adrenoceptor-mediated increase in Na-K-ATPase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278484
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  • 20
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of nicorandil in patients with normal and impaired renal function (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 203-207 
    Details
    ISSN: 1432-1041
    Keywords: Nicorandil ; pharmacokinetics ; angina pectoris ; uraemia ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of oral nicorandil 20 mg 12 hourly for 9 doses was evaluated in 21 hospitalized patients with angina pectoris due to coronary heart disease and with normal and impaired renal function. Patients were divided into 3 groups based on creatinine clearance (CLCr): GROUP I (n=6) 〉 80 ml/min, GROUP II (n=8) 20–80 ml/min, and GROUP III (n=7) 〈 20 ml/min. After the first dose, the total clearance of nicorandil (CL) value did not change with increasing renal failure and so was not dependent on creatinine clearance. After the last dose CL was 51 l·h−1 in Group I, 44 l·h−1 in Group II and 56 l·h−1 in Group III, and it was not related to creatinine clearance. The percentage of the dose excreted in the urine was 0.4%. No significant difference was noted in any of the other pharmacokinetic parameters examined in the three groups, not even on comparing values obtained on the first and last days of treatment. The findings suggest that there is no need to change the dose of nicorandil in subjects with different degrees of renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278485
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  • 21
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of sublingual and oral alprazolam in the post-prandial state (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 439-443 
    Details
    ISSN: 1432-1041
    Keywords: Alprazolam ; benzodiazepines ; pharmacokinetics ; pharmacodynamics ; sublingual dosage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We gave 12 healthy male volunteers 1 mg of alprazolam or placebo on three occasions after a standard breakfast in a double-blind, randomized, single-dose, three-way crossover study. The three trials were: (a) oral alprazolam and sublingual placebo; (b) oral placebo and sublingual alprazolam; (c) placebo by both routes. Plasma alprazolam concentrations during 24 h after each dose were measured by electron-capture gas-liquid chromatography. Peak plasma concentrations were reached later after sublingual than oral dosage (2.8 vs 1.8 h, P〈0.01). Other kinetic variables were not significantly different: peak plasma concentration, 11.3 vs 12.0 ng·ml−1; elimination half-life, 12.5 vs 11.7 h; and total area under the plasma concentration versus time curve, 197 vs 186 h·ng·ml−1. Pharmacodynamic measures showed that sublingual and oral alprazolam both produced sedation, fatigue, impaired digit symbol substitution, slowing of reaction time, and impairment of the acquisition and recall of information. These changes were initially observed at 0.5 h after dosage and lasted up to 8 h. In general the two routes were significantly different from placebo but not from each other.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280132
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  • 22
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ethanol in plasma and whole blood: estimation of total body water by the dilution principle (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 445-448 
    Details
    ISSN: 1432-1041
    Keywords: Ethanol ; whole blood ; plasma ; total body water ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of ethanol in plasma was 120 mg·dl−1 compared to 108 mg·dl−1 for whole blood. The disappearance rate of ethanol from plasma was 18.6 mg·dl−1·h−1 compared to 17.0 mg·dl−1·h−1 for the whole blood concentration-time data. The apparent volume of distribution of ethanol (Vz) was 0.54 l·kg−1 according to plasma kinetics compared to 0.59 l·kg−1 for the kinetics derived from whole blood. The mean area under the curve (AUC) was 294 mg·dl−1×h for plasma kinetics compared to 266 mg·dl−1×h for whole blood. The TBW was 40.9 l or 50.9% of body weight for the plasma concentration-time data. This agreed well with the 40.3 l or 50.1% of body weight obtained using whole blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280133
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  • 23
    Electronic Resource
    Electronic Resource
    High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 85-88 
    Details
    ISSN: 1432-1041
    Keywords: Methylprednisolone ; Rheumatoid arthritis ; bioavailability ; pharmacokinetics ; clinical response ; pulse steroid therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu MedrolR, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314925
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  • 24
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 89-93 
    Details
    ISSN: 1432-1041
    Keywords: Acetyl-L-carnitine ; Senile Dementia of Alzheimer Type ; pharmacokinetics ; plasma concentration ; cerebrospinal fluid concentration ; carnitine metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg·kg−1 i.v. given twice for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 2.0 g/day p.o. given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the i.v. bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 h and 1.73 h, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. It is concluded that i.v. and oral administration of multiple doses of ALC can increase its plasma and CSF concentration in patients suffering from Alzheimer's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314926
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  • 25
    Electronic Resource
    Electronic Resource
    Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 95-99 
    Details
    ISSN: 1432-1041
    Keywords: Ofloxacin ; Haemodialysis ; ofloxacin metabolites ; pharmacokinetics ; multiple doses ; dosage selection ; renal failure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg·1−1) and trough levels (1.6 mg·1−1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2β) and during the haemodialysis session (t1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min−1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2β of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314927
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  • 26
    Electronic Resource
    Electronic Resource
    The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 121-125 
    Details
    ISSN: 1432-1041
    Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278469
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  • 27
    Electronic Resource
    Electronic Resource
    Effect of tetracycline on mefloquine pharmacokinetics in Thai males (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 567-569 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; Tetracycline ; Thai subjects ; Thai subjects ; drug interaction ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with tetracycline has been studied in 20 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with tetracycline (1600 vs 1160 ng · ml−1), as well as a significantly reduced terminal half-life (14.4 vs 19.3 days), mean residence time (11.9 vs 16.0 days) and volume of distribution at steady state (13.3 vs 19.91 · kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 7 days was significantly increased by tetracycline (6.18 vs 4.76 μg · ml−1 · day). The changes in mefloquine disposition after tetracycline treatment are probably due to a reduction in enterohepatic recycling. The initial increase in mefloquine AUC without an apparent increase in side-effects suggests that this combination may have a place in the treatment of multi-drug resistant falciparum malaria.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02285105
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  • 28
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of cyclosporine in hyperlipidaemic long-term survivors of heart transplantation (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 161-165 
    Details
    ISSN: 1432-1041
    Keywords: Cyclosporine ; Hyperlipidaemia ; heart transplantation ; fenofibrate ; fenofibric acid ; pharmacokinetics ; drug interaction ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng·ml−1), Cmax (812 ng·ml−1 by RIA and 757 ng·ml−1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740664
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  • 29
    Electronic Resource
    Electronic Resource
    Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 219-222 
    Details
    ISSN: 1432-1041
    Keywords: Thiamine ; pharmacokinetics ; analytical method ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A novel liquid chromatographic method for the determination of thiamine in plasma has been developed and has been used to study plasma thiamine concentrations after multiple dosage regimens for 11 days. The method involves purification, concentration and analytical separation of thiochrome on-line, using a switching column system. Ten healthy men were given 500 mg thiamine i.m. once a day (Group 1) and ten were given 250 mg p.o. every 12 h (Group 2). The times to reach steady state (7 and 5.6 days for Groups 1 and 2, respectively) were not different (P〉0.05). The mean elimination half-life was 1.8 days. The mean minimum steady-state concentration after the oral regimen (23 μg·l−1) was 78% of that after the intramuscular regime (29 μg·l−1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278489
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  • 30
    Electronic Resource
    Electronic Resource
    Investigation of a possible pharmacokinetic interaction between ibopamine and isosorbide-5-mononitrate (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 549-552 
    Details
    ISSN: 1432-1041
    Keywords: Ibopamine ; Isosorbide-5-mononitrate ; pharmacokinetics ; drug interaction ; healthy volunteers ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between isosorbide-5-mononitrate (5-ISMN) and epinine, the active metabolite of ibopamine, has been investigated in 8 healthy male subjects given single doses of 200 mg ibopamine and 20 mg 5-ISMN, separately and together. The plasma 5-ISMN concentration-time profile was the same whether 5-ISMN was administered concomitantly with ibopamine or alone [AUC(o-t): 2.24 μg·ml−1·h after 5-ISMN alone, 2.16 μg·ml−1·h after 5-ISMN + ibopamine]. The plasma concentrations of total and free epinine and the urinary recovery of total epinine, homovanillic acid and dihydroxyphenylacetic acid, too, were not different when ibopamine was administered alone or concomitantly with 5-ISMN. The intake of ibopamine did not change the blood pressure and heart rate. The decrease in diastolic blood pressure induced by 5-ISMN was not influenced by concomitant intake of ibopamine. The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between 5-ISMN and ibopamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314867
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  • 31
    Electronic Resource
    Electronic Resource
    Metamizole-furosemide interaction study in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 593-598 
    Details
    ISSN: 1432-1041
    Keywords: Metamizole ; Furosemide ; prostaglandins ; drug interaction ; adverse effects ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and pharmacodynamic interactions between metamizole (dipyrone) and furosemide were investigated in 9 of 12 healthy female subjects able to complete the study. They received oral metamizole 3×1 g for 3 days or placebo (cross-over) and on the last day of both study periods furosemide 20 mg IV. On the last two days a balanced sodium diet (120 mEq) and on Day 3 an oral water load (600 ml) were given. Metamizole significantly inhibited basal urine flow, whereas the fractional excretion of sodium and chloride and the 12 h-GFR remained unchanged. Metamizole significantly reduced furosemide clearance (175 vs 141 ml · min−1), furosemide-stimulated plasma renin activity (1.42 vs 0.79 ng AI · ml−1 · h−1) and the urinary excretion of prostacyclin metabolites and of prostaglandin F2α (by 70–81%). The renal clearance and terminal half-life of furosemide, peak renal chloride and volume excretion were unchanged. Thus, metamizole did not interact with the renal excretion and the diuretic effect of furosemide, although prostaglandin synthesis was significantly reduced.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265921
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  • 32
    Electronic Resource
    Electronic Resource
    Rectal bioavailability of 6-mercaptopurine in children with acute lymphoblastic leukaemia: partial avoidance of “first-pass” metabolism (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 619-622 
    Details
    ISSN: 1432-1041
    Keywords: 6-Mercaptopurine ; suppository ; bioavailability ; acute lymphoblastic leukaemia ; children ; interindividual variability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and the area under the plasma concentration-time curve (AUC) values of 6-mercaptopurine (6-MP) were determined in a balanced crossover study of oral (powder) and rectal (macrogol suppository) administration to 5 children with acute lymphoblastic leukaemia (ALL). The AUC (538.6 ng · h · ml−1) after the rectal dose of 30 mg/m2 was approximately 1.5-times of that (365.5 ng · h · ml−1) after the oral dose of 87.5 mg/m2. The coefficients of variation of interindividual variability of the AUCs were 21.5% and 32.3%, respectively. The relative bioavailability of the macrogol suppository compared to the powder was approximately 4.39. These findings indicate that rectal administration of 6-MP could avoid the first-pass effect of this drug in the alimentary canal and/or liver, resulting in a large AUC of 6-MP, and so could reduce interindividual variability in plasma 6-MP concentrations. Rectal administration of 6-MP may be more effective than empirical oral dosing for the treatment of children with ALL, especially for patients with nausea and/or vomiting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265925
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  • 33
    Electronic Resource
    Electronic Resource
    Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 635-639 
    Details
    ISSN: 1432-1041
    Keywords: Vancomycin ; Haemodialysis ; highflux membranes ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Vancomycin is usually given only once a week to haemodialysis (HD) patients. If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week. In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g. Concentrations were determined by fluorescence polarisation immunoassay. At a blood flow of 219 ml·min−1, HD clearance of vancomycin was 62.3 ml·min−1. Immediately after dialysis plasma concentrations were 38% lower than predialysis levels. However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis. 3 HD treatments in 1 week removed about one third of the initial dose. After one week 15 of 18 patients still had a therapeutic plasma level (〉5 μg·ml−1). In conclusion, polysulfone membranes show high clearance of vancomycin. However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood. Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265928
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  • 34
    Electronic Resource
    Electronic Resource
    Effect of treatment at night with S-1452, a thromboxane A2 receptor antagonist, on the morning rise in platelet aggregation (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 501-505 
    Details
    ISSN: 1432-1041
    Keywords: S-1452 ; thromboxane A2 receptor antagonist ; nocturnal dosage ; platelet aggregation ; circadian rhythm ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is well known that platelet aggregation shows a morning rise, which may contribute to the increase in the onset of ischaemic heart diseases during the morning period. The present study was undertaken to determine whether nocturnal dosage with S-1452, a thromboxane AZ receptor antagonist, would blunt the morning rise in platelet aggregability. S-1452 50 mg or placebo were given orally to 8 healthy subjects at 10.00 h (day trial) or 22.00 h (night trial) according to a cross-over design. Plasma concentrations of S-1452 and its metabolites, bisnor-( + )-S-145 and tetranor-(+ )-S-145, and platelet aggregation were determined during the 12-hour period following the dose. Mean plasma concentrations of S-1452, bisnor-( + )-S-145 and tetranor-(+ )-S-145 during the absorption phase were lower after the nocturnal dose than after the morning dose. The maximum plasma concentration and area under the plasma concentration-time curve of the compounds were also lower and the time to the maximum concentration were delayed after the treatment at night. A morning rise in platelet aggregation was observed following placebo treatment. The inhibitory effect of S-1452 on platelet aggregation was observed at 3 hours and persisted for up to 9 h in both trials. The results suggest that S-1452 is absorbed more slowly after the nocturnal dose than after the morning dose. However nocturnal treatment with 50 mg S-1452 may blunt the morning rise in platelet aggregability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02285091
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  • 35
    Electronic Resource
    Electronic Resource
    Intracolonic bioavailability of human calcitonin in man (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 527-531 
    Details
    ISSN: 1432-1041
    Keywords: Calcitonin ; Colonic administration ; Bioavailability ; pharmacokinetics ; pharmacodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Human calcitonin (hCT) injected into the lumen of the descending colon of normal human subjects was absorbed within minutes and could be recognized intact in plasma as shown by RIA in combination with reverse-phase HPLC. The absorption was low and variable, with bioavailabilities ranging from 0.01% to 2.7% relative to intravenously administered hCT (area under the concentrationtime curve). With intravenous hCT serum calcium was lowered and the fractional urinary excretion of calcium, phosphorus, sodium and chloride was significantly stimulated. With the intracolonic hCT, the fractional urinary excretions of calcium, sodium and chloride were also marginally stimulated relative to intracolonic vehicle (placebo). In conclusion, hCT is absorbed intact from the colon, but the bioavailability is low and highly variable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02285096
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  • 36
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and blood pressure effects of carvedilol in patients with chronic renal failure (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 85-88 
    Details
    ISSN: 1432-1041
    Keywords: Hypertension ; Carvedilol ; chronic renal failure ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51–90 ml · min−1; II 26–50 ml · min−1; III 4–25 ml · min−1. The area under plasma level time curve AUC, the elimination half-life t/12, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02280760
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  • 37
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    Electronic Resource
    The pharmacokinetics of tiopronin and its principal metabolite (2-mercaptopropionic acid) after oral administration to healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 93-95 
    Details
    ISSN: 1432-1041
    Keywords: Tiopronin ; 2-mercaptopropionic acid ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of tiopronin and its principal metabolite, 2-mercaptopropionic acid (2-MPA) in healthy volunteers after the oral administration of 500 mg (2 Acadione® tablets), followed by simultaneous assay of the two compounds in plasma over a period of 48 h using a new method (emission of fluorescence after HPLC and post-column derivatization by pyrene-maleimide). The absorption of tiopronin was slow (tmax between 4 and 6 h) and the plasma concentrations subsequently fell biexponentially. The principal metabolite 2-MPA appeared later in the plasma (tmax between 10 and 12 h after a lag-time of 3 h) then disappeared monoexponentially. About 15% of the tiopronin was metabolized to 2-MPA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02280762
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  • 38
    Electronic Resource
    Electronic Resource
    Lack of effect of omeprazole, cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 209-212 
    Details
    ISSN: 1432-1041
    Keywords: Ethanol ; gastric acid inhibition ; pharmacokinetics ; antisecretory drugs ; omeprazole ; ranitidine ; cimetidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment. Male medical students (n=12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments. The peak blood ethanol concentration of 21.9 to 22.8 mmol·l−1 occurred at 64 to 70 min after the end of drinking. The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol·l−1·h−1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g·h−1. The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l·kg−1, corresponding to a mean total body water of 441 (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol·l−1·h for the four treatments. It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278486
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  • 39
    Electronic Resource
    Electronic Resource
    Absence of interaction between tenoxicam and warfarin (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 227-229 
    Details
    ISSN: 1432-1041
    Keywords: Tenoxicam ; Warfarin ; drug interaction ; pharmacokinetics ; anticoagulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278491
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  • 40
    Electronic Resource
    Electronic Resource
    The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 173-177 
    Details
    ISSN: 1432-1041
    Keywords: Enalapril ; Hydrochlorothiazide ; pharmacokinetics ; renal impairment ; old patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomized, cross-over, single-dose study of 19 elderly hypertensive patients (aged 62–84 y, SBP 〉 160 mm Hg, DBP 〉 100 mm Hg, creatinine clearance 11–93 ml·min−1) we have studied the pharmacokinetics of the angiotensin converting enzyme (ACE) inhibitor enalapril after a single oral dose of either 10 mg enalapril or 10 mg enalapril + 25 mg hydrochlorothiazide. The pharmacokinetics of enalapril were unaffected by hydrochlorothiazide, but there was a significant reduction in renal clearance and a significant increase in AUC(0–24 h) of enalaprilat after hydrochlorothiazide, resulting in higher serum concentrations of the active drug. This was independent of the individual degree of renal impairment and might be due either to an initial reduction of GFR by hydrochlorothiazide or to interference with the tubular secretion of enalaprilat. The relationships between serum enalaprilat and serum ACE activity were similar after both treatments, both consistent with a value for Ki of enalaprilat of about 0.1 nmol·l−1. Thus, serum ACE activity was not affected by hydrochlorothiazide but completely reflected the pharmacokinetics of enalaprilat in both treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740666
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  • 41
    Electronic Resource
    Electronic Resource
    Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine ebastine with ethanol in healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 179-184 
    Details
    ISSN: 1432-1041
    Keywords: Ebastine ; Ethanol interaction ; carebastine ; psychomotor performance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or placebo in a double-blind, crossover study for one week each. The subjects were tested for drug effects on Day 6 of each period, and for interactions of ebastine with ethanol (0.8 g·kg−1) on Day 7. On both days, the testing runs were done at baseline and at 2, 4, and 6 h after the drug. Performance was evaluated both objectively (digit symbol substitution, flicker fusion, Maddox wing, nystagmus, simulated driving, body balance) and subjectively (visual analogue scales) and with questionnaires. Venous blood samples were taken daily during maintenance and during each test run for assay of plasma carebastine. Blood ethanol concentrations were assayed with an Alcolmeter in the breath and directly in the blood. Plasma carebastine concentration reached a steady-state from Day 3 on; the mean concentrations in the morning were 92 µg·l−1 on Day 6 and 104 µg·l−1 on Day 7. The rise in plasma carebastine after an extra 20 mg of ebastine was accelerated but not increased by ethanol. Ebastine did not impair performance objectively or subjectively. It slightly improved body balance and reduced errors during simple tracking at 4 h. Blood ethanol concentrations peaked (mean 0.76 g·l−1) at 1.5 h after ethanol intake. Ethanol impaired performance in most objective tests and produced clumsiness, muzziness, and mental slowness, but little drowsiness. Ebastine neither modified the blood ethanol concentrations nor increased the effects of ethanol. We conclude that treatment with 20 mg ebastine once daily for one week provides steady concentrations of carebastine in plasma without impairment of skilled performance or important interactions with alcohol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740667
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  • 42
    Electronic Resource
    Electronic Resource
    Lack of interaction ofβ-methyldigoxin with ranitidine in patients with chronic congestive heart failure (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 205-206 
    Details
    ISSN: 1432-1041
    Keywords: β-Methyldigoxin ; Ranitidine ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740673
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  • 43
    Electronic Resource
    Electronic Resource
    The effect of haemodialysis on the pharmacokinetics of tenoxicam in patients with end-stage renal disease (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 197-199 
    Details
    ISSN: 1432-1041
    Keywords: Tenoxicam ; pharmacokinetics ; haemodialysis ; end-stage renal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of tenoxicam after single and multiple oral doses of 20 mg in five patients (2 men and 3 women) with end-stage renal disease undergoing haemodialysis. After a single dose, tenoxicam had a half-life (t1/2) of 33 h, an apparent clearance (CL·f−1) of 4.3 ml·min−1, and an apparent volume of distribution (Vz·f−1) of 11.8 l. The maximum tenoxicam concentration (Cmax) was 4.3 mg·l−1 at a median tmax of 1.7 h. There were no significant differences between the values calculated from the pre- or post-dialyser port plasma samples. Tenoxicam plasma concentrations measured during once daily dosing before and after haemodialysis showed that tenoxicam does not accumulate. Our findings suggest that dosage adjustment may not be required in patients with end-stage renal disease on haemodialysis taking tenoxicam.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740671
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  • 44
    Electronic Resource
    Electronic Resource
    Relationship between arterial and peripheral venous catecholamine plasma catecholamine concentrations during infusion of noradrenaline and adrenaline in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 245-249 
    Details
    ISSN: 1432-1041
    Keywords: Noradrenaline ; Adrenaline ; catecholamines ; pharmacokinetics ; healthy volunteers ; IV infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Noradrenaline and adrenaline were infused IV at 5 different rates (0.01–0.2 μg · kg · min− for 30 min to volunteers. The plasma catecholamine concentrations were determined by HPLC and electro-chemical detection. At the highest infusion rate, the arterial and venous plasma concentrations of noradrenaline increased from 1.18 to 44.1 nmol · l−1and from 1.14 to 31.9 nmol · l−1, respectively, and of adrenaline from 0.29 to 23.9 nmol · l−1 and from 0.28 to 19.3 nmol · l−1 respectively. The peripheral venous plasma concentration of noradrenaline averaged 76% of the arterial concentration, and of adrenaline it was 73%. There was a linear relationship between the peripheral venous and arterial plasma noradrenaline and adrenaline concentrations at therapeutic doses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02333017
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  • 45
    Electronic Resource
    Electronic Resource
    Pharmacokinetic profile of a novel slow release preparation of molsidomine (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 273-276 
    Details
    ISSN: 1432-1041
    Keywords: Molsidomine ; slow release ; pharmacokinetics ; in vitro/in vivo correlation ; pharmacokinetics ; healthy volunteers ; dissolution profile
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A novel slow release preparation containing 24 mg molsidomine has been investigated in 6 healthy subjects. Individual concentration/time-profiles after the tablet showed two separate concentration peaks at 2.2 h and 15.0 h. The relative bioavailability of the slow release preparation in comparison to an aqueous solution of molsidomine was 0.67. The in vivo dissolution profile revealed either a progressive decrease in dissolution velocity caused by altered physico-chemical conditions in the ileum and the colon or a progressive reduction in the absorption constant. In all subjects deconvolution revealed a punctual increase in absorption about 15 h post-dose, coinciding with the second peak of the concentration/time-profile. Therapeutic plasma levels of molsidomine (〉 5 ng · ml−1 were not maintained over 24 h by this slow release formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02333022
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  • 46
    Electronic Resource
    Electronic Resource
    Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 445-447 
    Details
    ISSN: 1432-1041
    Keywords: Captopril ; Digitoxin ; impedance cardiography ; drug interaction ; healthy volunteers ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The chronic oral administration of 0.07 mg digitoxin o. d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95 % CI: −7.9 to −1.6 beats · min−1), in mean diastolic blood pressure (95 % CI: −8.3 to −0.4 mm Hg), shortening of the QTc-interval (95 % CI: −42 to −19 ms), shortening of the HR-corrected pre-ejection period PEPc (95 % CI: −16 to −1 ms) and electromechanical systole QS2c (95 % CI: −25 to −1 ms), and an increase in the impedance cardiographic Heather index (dZ/dtmax/RZ, 95 % CI: 0.3 to 4.3) relative to the baseline measurements before digitalisation. The concomitant administration of 25 mg oral captopril b. d. did not significantly alter these responses relative to the concomitant double-blind administration of placebo, nor did it alter the pharmacokinetic characteristics of plasma digitoxin at steady state. Thus, no relevant change in the pharmacokinetic and pharmacodynamic characteristics of chronically administered digitoxin were induced by concomitant treatment with captopril.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02220626
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  • 47
    Electronic Resource
    Electronic Resource
    Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 237-256 
    Details
    ISSN: 1432-1041
    Keywords: Non-steroidal anti-inflammatory drugs ; Enantioselective ; Enantiomers ; pharmacodynamics ; pharmacokinetics ; stereoselective
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266343
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  • 48
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    Electronic Resource
    Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine — and its potential clinical relevance (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 313-317 
    Details
    ISSN: 1432-1041
    Keywords: Dihydropyridine ; Felodipine ; availability ; flavonoids ; dietary interaction ; pharmacokinetics ; pharmacodynamics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol · l−1, and in the AUC from 23 to 65 nmol · h · l−1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (−9%) than did water (0%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266354
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  • 49
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of midazolam during continuous infusion in critically ill neonates (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 329-332 
    Details
    ISSN: 1432-1041
    Keywords: Midazolam ; Fentanyl ; Neonates ; pharmacokinetics ; sedation drug interaction ; hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children. An IV bolus (0.2 mg·kg−1) immediately followed by continuous infusion of 0.06 mg·kg−1·h−1 was administered to 15 critically ill neonates at a gestational age of 32.8 weeks, who required sedation for mechanical ventilation. Heart rate and blood pressure were closely monitored. Hypotension occurred in 4 patients after the bolus dose or during the continuous infusion. Three of them had also been given fentanyl. Individual pharmacokinetic parameters were calculated: plasma clearance was 3.9 ml·min−1, elimination half-life was 12.0 h. Because of its short half-life compared to diazepam, midazolam may be used during the neonatal period to achieve rapid, brief sedation. However, it should be administered cautiously to neonates, particularly in premature infants, or if fentanyl is also given.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266357
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  • 50
    Electronic Resource
    Electronic Resource
    Theophylline steady state pharmacokinetics is not altered by omeprazole (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 343-345 
    Details
    ISSN: 1432-1041
    Keywords: Omeprazole ; Theophylline ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of omeprazole treatment on theophylline pharmacokinetics was studied in eight, non-smoking healthy male volunteers during repeated administration of a slow release formulation of theophylline. In a randomized double-blind cross-over study, the subjects received theophylline 5 mg·kg−1 per day with omeprazole 20 mg per day or identical placebo during two periods, each of 7 days, separated by a washout period of 7 days. The oral clearance of theophylline remained unchanged whether it was administered alone or with omeprazole (54.2 ml·min−1). The average urinary excretion of theophylline and its metabolites, 1,3 dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX), 1-methyluric acid (1-MU) amounted to 9%, 32%, 12% and 22% of the administered dose, respectively, and no significant change occured during concomitant treatment with omeprazole. Thus, the formation and clearance of the metabolites was not altered by omeprazole. Consequently, omeprazole in the recommended dose of 20 mg daily can safely be administered to patients on theophylline therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266361
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  • 51
    Electronic Resource
    Electronic Resource
    Disposition kinetics and concentration-effect relationship of metipranolol in patients with cirrhosis and healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 337-340 
    Details
    ISSN: 1432-1041
    Keywords: Metipranolol ; Liver cirrhosis ; pharmacokinetics ; pharmacodynamics ; beta-adrenoreceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics and heart rate reducing effect of deacetylmetipranolol (DMP), the active form of the β-adrenoreceptor blocking agent metipranolol (MP), administered as a single 40 mg oral dose have been compared in 6 patients with cirrhosis and 6 healthy volunteers. The mean maximal DMP concentration was significantly higher and the time to reach the peak level shorter in the patients compared to the healthy subjects. There was also a significantly higher AUC of DMP, a shorter half-life of the rapid phase of the decline in DMP concentrations, a smaller central compartment and lower apparent DMP clearance in patients. A correlation with the albumin level was observed in cirrhotics for individual values of apparent DMP clearance (r=0.92) and AUC (r=-0.89). The maximal reduction in heart rate was recorded in patients at plasma DMP levels which were already significantly lower than the peak levels. Median inhibitory concentrations (IC50) and maximum possible heart rate reductions (Δ HRmax), obtained by fitting individual plots of the plasma DMP concentration-effect relationship to the inhibitory Emax model in the postdistributional phase of DMP disposition were significantly higher in cirrhotics than in healthy subjects. It is conjectured that down-regulation of adrenoreceptors due to chronic sympathetic activation in hepatic cirrhosis contributes to decreased sensitivity to the reduction in heart rate following a single dose of the beta-blocker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266359
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  • 52
    Electronic Resource
    Electronic Resource
    Influence of food on serum ambenonium concentration in patients with myasthenia gravis (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 371-374 
    Details
    ISSN: 1432-1041
    Keywords: Ambenonium chloride ; Myasthenia gravis ; dietary effect ; serum concentration ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non-fasting state. The AUC (0–3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the non-fasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280120
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  • 53
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    Electronic Resource
    Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 423-427 
    Details
    ISSN: 1432-1041
    Keywords: Nitrendipine ; enantiomers ; stereoselectivity ; Renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml·min−1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280129
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  • 54
    Electronic Resource
    Electronic Resource
    Chloroquine levels in blood during chronic treatment of patients with rheumatoid arthritis (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 429-433 
    Details
    ISSN: 1432-1041
    Keywords: Chloroquine ; Rheumatoid arthritis ; desethylchloroquine ; bisdesethylchloroquine ; blood levels ; toxicity ; therapeutic activity ; dose-effect relationship ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in the steady state blood concentrations of chloroquine (range 36.6 to 3895 ng·ml−1) and its two main biotransformation products; the latter represented, respectively, 47.7% and 12.9% of the concentration of chloroquine. This finding shows the need for further studies in view of the known toxic effects of chloroquine and the inevitable accumulation due to the exceptionally long residence time of the compound and its metabolites. The main requirement, which has not yet been met, for adding chloroquine to the list of drugs for which therapeutic drug monitoring is useful, is the lack of information about its mechanism of action, and consequently the dose-effect relationships of its therapeutic and toxic actions. Regular ophthalmic examination, in particular, is strongly recommended. The relatively high concentrations of desethylchloroquine and bisdesethylchloroquine found during chronic treatment show the need for more information about the therapeutic value and adverse effects of the metabolites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280130
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  • 55
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    Electronic Resource
    Elevated plasma nilvadipine concentration after single and chronic oral administration to patients with chronic liver disease (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 475-479 
    Details
    ISSN: 1432-1041
    Keywords: Calcium channel blocker ; Nilvadipine ; blood pressure ; liver disease ; pharmacokinetics ; pharmacodynamics ; cirrhosis ; hepatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fourteen normotensive patients with liver disease (6 with cirrhosis and 8 with chronic hepatitis) and 7 healthy volunteers were given a single oral dose of nilvadipine 2 mg. In addition, nilvadipine 4 mg was administered orally twice daily for several months to 6 hypertensive patients with mild liver dysfunction and 18 hypertensives with normal liver function. A significant increase in plasma nilvadipine was found in the patients with cirrhosis as compared both to the normal and chronic hepatitis subjects; the time to peak concentration was similar among the three groups. The peak plasma nilvadipine concentration was closely correlated both with the serum albumin level and the retention of indocyanine green. Changes in blood pressure, pulse rate and various vasoactive hormones following a single oral dose of nilvadipine did not differ between the groups. Thus, an increase in plasma nilvadipine relative to the level in normal subjects was demonstrated in patients with cirrhosis following a single oral dose, as well as in patients with slight liver dysfunction following long-term oral administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314853
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  • 56
    Electronic Resource
    Electronic Resource
    Digoxin-interactions in man: Spironolactone reduces renal but not biliary digoxin clearance (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 481-485 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; Spironolactone ; drug interaction ; biliary clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg·d−1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 × oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P=0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314854
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    Pharmacokinetics of vinorelbine in man (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 545-547 
    Details
    ISSN: 1432-1041
    Keywords: Vinorelbine ; anti-neoplastic agents ; vinca alkaloids ; pharmacokinetics ; lung neoplasms ; HPLC ; assay method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of vinorelbine has been investigated by a new HPLC method in 8 cancer patients receiving 8 weekly doses (30 mg·m−2) administered by brief infusion (15 min). The plasma concentration-time curves showed a tri-exponential decay with a long terminal half-life (44.7 h) and a high volume of distribution (Vz=75.61·kg−1). The concentrations after the 8th infusion were significantly lower than after the 1st infusion, but without significant modification of CL (1.28 l·h−1·kg−1) or AUC (0.80 mg·l−1·h). The pharmacokinetic parameters exhibited wide inter-individual variations. The results are consistent with those of previous RIA studies, although the HPLC method appears to be more specific and more precise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314866
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  • 58
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    The postoperative pharmacokinetics of codeine (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 663-666 
    Details
    ISSN: 1432-1041
    Keywords: Morphine ; Codeine ; drug metabolism ; pharmacokinetics ; systemic availability ; individual variability ; post-operative state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolism and systemic availability of codeine have been studied in 12 patients after cholecystectomy. They were given 20 mg codeine as an IV bolus dose on the first day after surgery and 50 mg codeine as a single oral on the fourth day after surgery. Codeine had a medium to high extraction ratio and a total plasma clearance of 10.8 (4.3) ml·min−1·kg−1. The clearance varied fourfold between subjects. All the patients were extensive metabolizers with regard to the debrisoquine/sparteine polymorphism, as tested using dextromethorphan as the probe drug. Nevertheless, the formation of morphine from codeine was very small and plasma morphine concentrations were below the detection limit of 3.3 nmol·1−1 (1 ng·ml−1). As a corollary, the morphine/codeine ratio in the the concentration-time curves was less than 3% in all the patients. The systemic availability of codeine varied extensively between subjects (range 12–84%). This might partly explain differences in the dose of codeine required as an analgesic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265933
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  • 59
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    The pharmacokinetics of nifurtimox in chronic renal failure (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 671-673 
    Details
    ISSN: 1432-1041
    Keywords: Nifurtimox ; Changas' disease ; renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of nifurtimox, a drug used in the treatment of Trypanosoma cruzi infections, has been studied in seven patients with chronic renal failure undergoing haemodialysis, and in seven healthy subjects. Each subject took nifurtimox 15 mg·kg−1 orally and blood samples were obtained for 10 h after administration. Nifurtimox in serum was analyzed by HPLC. The patients with chronic renal failure had a higher Cmax than the control subjects due to a change in systemic availability. An alternative explanation would be that both the distribution volume and the clearance had changed. The mean half-life in the patients with chronic renal failure was similar to that in the healthy subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265935
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  • 60
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    Lack of pharmacokinetic interaction between moxonidine and hydrochlorothiazide (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 209-210 
    Details
    ISSN: 1432-1041
    Keywords: Moxonidine ; Hydrochlorothiazide ; pharmacokinetics ; drug interaction ; steady-state ; healthy volunteers ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740675
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  • 61
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    Altered pharmacokinetics of lignocaine after epidural injection in Type II diabetics (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 269-271 
    Details
    ISSN: 1432-1041
    Keywords: Lignocaine ; diabetes mellitus ; pharmacokinetics ; epidural anaesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of lignocaine has been compared after epidural anaesthesia in diabetics and nondiabetic patients. Epidural lignocaine 8 mg · kg−1 was given to 8 well controlled Type II diabetic and 8 nondiabetic patients and the plasma drug concentration in serial blood samples were measured by HPLC. The plasma level of lignocaine was lower in diabetics compared to non-diabetics. The peak level was attained at 20 min in both groups. The clearance of the drug was significantly higher, (39,9 vs 16,7 ml · min− · kg−) associated with a decreased elimination half-life and mean residence time. The study suggests that the rate of absorption of lignocaine is not altered after epidural administration and that its hepatic metabolism is increased in diabetics compared to non-diabetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02333021
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  • 62
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    Pharmacokinetic estimations from microdialysis data (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 289-294 
    Details
    ISSN: 1432-1041
    Keywords: Microdialysis ; Drug concentration ; parameter estimation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Microdialysis has recently been adapted for sampling the extracellular fluid of various organs in order to measure drug concentrations, and the first clinical application has been published. My aim here is to provide simple rules about how to analyse pharmacokinetic data from such studies. The plotting of data on a time scale and the estimation of C (0) and slopes is not a trivial problem when multicompartmental models are assumed or sampling intervals are unequal. I have developed formulae and algorithms to solve the problem. A simple rule of thumb is given, suggesting when these formulae need to be applied. It is shown that the calculations of half-life and slopes is similar to standard methods for equal sample intervals and that calculation of AUC and clearance may be even more accurate for microdialysis data than for ordinary blood sampling, because of the time-integral character of the dialysis method. I have dealt with both zero-order and first-order kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02333025
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  • 63
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    Pharmacokinetics of pirmenol in young and elderly subjects (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 437-439 
    Details
    ISSN: 1432-1041
    Keywords: Pirmenol ; pharmacokinetics ; elderly subjects ; age effect ; adverse effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29 % higher and CL/f was 22 % lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, λz, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02220624
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  • 64
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    The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 441-443 
    Details
    ISSN: 1432-1041
    Keywords: Flecainide ; quinidine ; pharmacokinetics ; metabolism inhibition ; drug interaction ; renal transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the effects of quinidine on ECG intervals and on the pharmacokinetics of flecainide and its two metabolites in 6 healthy men in an open randomized crossover study. Flecainide acetate (150 mg) was given as a constant rate i. v. infusion over 30 min. Quinidine (50 mg orally), given the previous evening, did not change the volume of distribution of flecainide (7.9 vs 7.41·kg−1), but significantly increased its half-life (8.8 vs 10.7 h). This was attributable to a reduction in total clearance (10.6 vs 8.1 ml·min−1·kg−1), most of it being accounted for by a reduction in non-renal clearance (7.2 vs 5.2 ml·min−1·kg−1). The excretion of the metabolites of flecainide over 48 h was significantly reduced. These findings suggest that quinidine inhibits the first step of flecainide metabolism, although it may also reduce its renal clearance, but to a lesser extent (3.5 vs 2.9 ml·min−1·kg−1). The effects of flecainide on ECG intervals were not altered by quinidine. Thus, quinidine tends to shift extensive metabolizer status for flecainide towards poor metabolizer status and may also alter its renal excretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02220625
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  • 65
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    Craniofrontonasal dysplasia (1992)
    Springer
    European journal of pediatrics 151 (1992), S. 837-841 
    Details
    ISSN: 1432-1076
    Keywords: Frontonasal dysplasia ; Craniosynostosis ; Genetics ; X chromosome ; Psychomotor development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report on nine patients with craniofrontonasal dysplasia (CFND). Seven classical cases had facial features suggestive of frontonasal dysplasia and coronal craniosynostosis. Extracranial abnormalities such as brittle nails with prominent longitudinal grooves or syndactyly of fingers and toes were observed in individual patients. In two families the father of classical cases showed a milder pattern of abnormalities, consistent with the diagnosis. We present a 2- to 13-year follow-up on our patients. Hypotonia and laxity of joints are common and may necessitate supportive measures. Mild developmental delay was noted in three out of six classical cases studied in detail. Unlike almost all other X-linked disorders, clinical expression in CFND is generally much more severe in females than in males. In contrast to previous reports of this condition, one of our severely affected cases is a male.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01957936
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  • 66
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    Genetic and immunologic analysis of a family containing five patients with common-variable immune deficiency or selective IgA deficiency (1992)
    Springer
    Journal of clinical immunology 12 (1992), S. 406-414 
    Details
    ISSN: 1573-2592
    Keywords: Genetics ; immune deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A family with 13 members included 2 subjects with selective IgA deficiency (IgA-D) and 3 subjects with common-variable immune deficiency (CVID), diseases which usually occur sporadically. Reciprocal combinations of B and T cellsin vitro between one normal and two immune-deficient family members and normal subjects revealed that defective Ig synthesis was determined by the B cells, while the patient T cells functioned normally. Normal T helper and suppressor function was demonstrated even in one patient with CVID who developed a T-cell lymphoproliferative disorder associated with elevated IgM; this patient's B cells made only IgMin vitro. Immune deficiencies were inherited in this family in a pattern consistent with an autosomal dominant trait with incomplete penetrance. All the immune-deficient patients in this family possessed at least one copy of an MHC haplotype previously shown to be abnormally frequent in IgA-D and CVID: HLA-DQB1*0201, HLA-DR3, C4B-Sf, C4A-deleted, G11-15, Bf-0.4, C2-a, HSP70-7.5, TNFα-5, HLA-B8, and HLA-A1. The patient who developed the lymphoproliferative disorder was homozygous for this haplotype. Four immunologically normal members, one of whom was 80 years old, also possessed this MHC haplotype, indicating that its presence is not sufficient for disease expression. A small segment of another MHC haplotype associated with Ig deficiency in the population also occurred in this family, but it was not associated with immune deficiency. The presence of neutral amino acids at position 57 of DQβ, previously correlated with IgA-D, was associated with disease in this family approximately to the same degree reported previously in unrelated patients. Thus the expression of immunodeficiency in individuals bearing a disease-associated MHC haplotype appears to require either additional genes or an environmental trigger.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00918852
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  • 67
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    Type 2 (non-insulin-dependent) diabetes mellitus and glucose transporter gene (GLUT 1 andGLUT 4) polymorphism (1992)
    Springer
    Acta diabetologica 29 (1992), S. 110-112 
    Details
    ISSN: 1432-5233
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; Genetics ; Polymorphisms ; GLUT 4 ; GLUT 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucose transporter genes have been proposed as candidate genes for type 2 (non-insulin-dependent) diabetes mellitus. We chose to study the adult skeletal muscle glucose transporter gene (GLUT 4) andGLUT 1 in consideration of previous conflicting results obtained by different authors. We studied 68 patients with type 2 diabetes, and 66 non-diabetic controls matched for age, sex, and body mass index (BMI). Women and men were considered separately, according to BMI (≤24.0 and 〉24.0 for women; ≤25.0 and 〉25.0 for men). Allele and genotype frequencies were not significantly different in controls and in type 2 diabetic patients. ForGLUT 1 allele 1 and genotype x1x1 were more frequent, although not significantly (P=0.064 at χ2,P=0.025 at Fisher exact test) in overweight/obese diabetic women than in overweight/obese non-diabetic women. These data do not support the hypothesis that these genes play a major role in genetic susceptibility to type 2 diabetes mellitus, but suggest a possible association, at least in women, of allele 1 ofGLUT 1 with obese type 2 diabetes mellitus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572554
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  • 68
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    Renal function in primary hypertension (1992)
    Springer
    Acta diabetologica 29 (1992), S. 173-177 
    Details
    ISSN: 1432-5233
    Keywords: Erythrocyte ; Genetics ; Renal function ; Sodium transport systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies of kidney cross-transplantation in the Milan hypertensive strain of rats (MHS) and in its control strain (MNS) have demonstrated that the kidney has a causal role in the development of hypertension in this animal model. The same result was obtained in two other strains of rats with genetic hypertension. Patients receiving a kidney from a donor with hypertensive parents require more antihypertensive therapy than recipients of a kidney from a donor with a normotensive family. When MHS rats and a subset of patients with primary hypertension were compared with their appropriate controls, similar changes in kidney function and Na−K−Cl cotransport were observed. Offspring of hypertensive parents exhibit altered kidney function compared with their controls. Na−K−Cl co-transport in MHS rats is genetically determined and genetically associated with hypertension. In MHS rats the increase in Na−K−Cl co-transport seems to be linked to a cytoskeletal protein, adducin. In conclusion, a consistent sequence of events from a protein abnormality to cell and renal dysfunction may be proposed as being responsible for hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00573483
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  • 69
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    The expression of salt tolerance from Triticum tauschii in hexaploid wheat (1992)
    Springer
    Theoretical and applied genetics 84 (1992), S. 714-719 
    Details
    ISSN: 1432-2242
    Keywords: Wheat ; Salinity ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Accessions of Triticum tauschii (Coss.) Schmal. (D genome donor to hexaploid wheat) vary in salt tolerance and in the rate that Na+ accumulates in leaves. The aim of this study was to determine whether these differences in salt tolerance and leaf Na+ concentration would be expressed in hexaploid wheat. Synthetic hexaploids were produced from five T. tauschii accessions varying in salt tolerance and two salt-sensitive T. turgidum cultivars. The degree of salt tolerance of the hexaploids was evaluated as the grain yield per plant in 150 mol m-3 NaCl relative to grain yield in 1 mol m-3 NaCl (control). Sodium concentration in leaf 5 was measured after the leaf was fully expanded. The salt tolerance of the genotypes correlated negatively with the concentration of Na+ in leaf 5. The salt tolerance of the synthetic hexaploids was greater than the tetraploid parents primarily due to the maintenance of kernel weight under saline conditions. Synthetic hexaploids varied in salt tolerance with the source of their D genome which demonstrates that genes for salt tolerance from the diploid are expressed at the hexaploid level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00224174
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  • 70
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    Pharmacokinetics and cytotoxicity of B.3839, a molecular combination of 5-fluorouracil and N-(2-chloroethyl)-N-nitrosourea, in a mouse model (1992)
    Springer
    Investigational new drugs 10 (1992), S. 149-158 
    Details
    ISSN: 1573-0646
    Keywords: pharmacokinetics ; cytotoxicity ; molecular combination ; fluorouracil ; nitrosourea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary B.3839 is the prototype compound in a series of novel molecular combinations of chloroethylnitrosoureas and 5-fluorouracil(5-FU) and has been tested against MAC tumours in mice. Previous studies have shown it is moderately active against MAC15A and highly active against MAC13 though this activity is dependent on route of administration. The aim of this study was to determine whether bioavailability could explain this difference in anti-tumour activity. Plasma levels of B.3839 and 5-FU after i.p. and oral administration were measured using HPLC. Non tumour-bearing and MAC26 bearing mice gave almost identical plasma profiles after i.p. administration with the Cmax being 29.8 and 30.4μ gml−1 and t1/2 16 and 15 min. The AUCs were 15.3 and 13.9μg h ml−1 suggesting tumour load had no influence over plasma levels. Oral administration gave a much lower Cmax of 8.0μg ml−1 but an AUC of 15.2μg h ml−1 due to a longer terminal t1/2 (94 min) giving 99% bioavailability. Levels of 5-FU release from B.3839 by either route were considered too small to influence anti-tumour activity. Cytotoxicity assaysin vitro against the MAC lines gave IC70 values of 5.3, 13.8 and 8.6μg ml−1 for MAC 26,13 and 15A respectively after a one hour exposure. Bone marrow toxicity was shown to be less severe than that of TCNU which is currently in clinical trials. The results show bioavailability alone is not enough to explain tumour response. There appears to be a need for a threshold concentration (C) to be maintained for a period of time (t).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00877239
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    Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation (1992)
    Springer
    Journal of neuro-oncology 13 (1992), S. 291-299 
    Details
    ISSN: 1573-7373
    Keywords: dosage calculation ; intra-arterial chemotherapy ; neurotoxicity ; malignant glioma ; pharmacokinetics ; dosing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The frequency of both neurologic toxicity and therapeutic response due to intra-arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if ≥ 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra-arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172483
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  • 72
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    Physiological pharmacokinetic parameters for cis-dichlorodiammineplatinum(II) (DDP) in the mouse (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 95-99 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; physiological model ; cisplatin ; DDP ; cis-dichlorodiammineplatinum(II)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01143187
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    Evaluation of dose-related pharmacokinetics and pharmacodynamics of prednisolone in man (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 567-589 
    Details
    ISSN: 1573-8744
    Keywords: prednisolone ; pharmacokinetics ; pharmacodynamics ; corticosteroids ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of prednisolone were evaluated in normal male volunteers. Seven subjects completed 3 phases: 16.4−and 49.2−mg iv prednisolone, and a phase with no drug to assess baseline responses. Plasma concentrations of prednisolone and urine concentrations of prednisolone and 5 metabolites were assayed by HPLC. Protein binding of prednisolone was measured by ultrafiltration. The polyexponential disposition of free and total plasma prednisolone were evaluated and apparent parameters were compared between doses. Suppression of plasma cortisol and alterations in blood basophil and helper-T cell trafficking were used as pharmacodynamic indices. Pharmacodynamic models were used to relate total or free plasma prednisolone concentrations to each of these effects generating response parameters and IC50 (50% inhibitory) concentrations common to both doses. The pharmacokinetics of total drug were comparable to previous findings with CLand Vss increasing with dose. Free prednisolone exhibited slight capacitylimited elimination and distribution as CLand Vss decreased with the larger dose. Pharmacodynamic models jointly fitting all three phases characterized the suppression/trafficking phenomena equally well with use of total or free drug concentrations. In each case the models provided realistic values of parameters relating to steroid sensitivity-in particular IC50-and to the underlying physiology of the affected systems. This study comprehensively elucidates the complexities of prednisolone pharmacokinetics and demonstrates how plasma concentration-time profiles of total or free prednisolone can be utilized for evaluation of prednisolone pharmacodynamics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01064420
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    The distribution and some pharmacokinetic parameters of ivermectin in pigs (1992)
    Springer
    Veterinary research communications 16 (1992), S. 139-146 
    Details
    ISSN: 1573-7446
    Keywords: ivermectin ; pharmacokinetics ; pigs ; residues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ivermectin was injected subcutaneously into five pigs at the usual dose rate of 300 µg/kg and found to distribute well to all tissues and body fluids which were sampled 24 h post-injection. Ivermectin was detected in the contents and mucus at all levels of the gastrointestinal tract. The drug was excreted in bile, with high concentrations of the drug in the intestines and faeces. High concentrations of ivermectin were measured in skin, ears and ear wax, suggesting that the drug should be effective in the treatment of ectoparasitic infestations, particularly ear mites. The high lipid solubility of the drug may explain the high concentrations found in ear wax and skin. Ivermectin was also detected in the body fluids and tissues of an untreated pig penned with the treated animals. Direct contact appeared to be necessary for transfer of ivermectin from the treated to the untreated pig but coprophagia or urine drinking is a possible explanation. The pharmacokinetics of ivermectin administered subcutaneously at a dose rate of 300 µg/kg to six pigs were studied. There was marked individual variation in the pharmacokinetics of ivermectin. In one pig the area under the plasma concentration-time curve was particularly high. This may reflect individual variation in uptake and excretion of the drug. The mean elimination half-life of the drug was 35.2 h, suggesting that the drug is cleared slowly from pigs with drug detectable in plasma for 6–10 days. This persistence should allow a short period of protection before re-infection with parasites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01839011
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    The influence of age on the pharmacokinetics of aditoprim in pigs after intravenous and oral administration (1992)
    Springer
    Veterinary research communications 16 (1992), S. 355-364 
    Details
    ISSN: 1573-7446
    Keywords: aditoprim ; age ; bioavailability ; intestinal absorption ; pharmacokinetics ; pigs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Some pharmacokinetic parameters of aditoprim were determined in 3- and 6-month-old pigs. After intravenous administration of 5 mg/kg body weight, the mean total body clearance of the older pigs was smaller than that of the younger pigs. This difference was not reflected in the elimination half-life. After oral administration of 5 mg/kg body weight, the mean absorption rate constant was smaller and the mean absorption half-life was longer in the older pigs. The age-related changes in the pharmacokinetics of aditoprim were not sufficiently pronounced to suggest the necessity of modifying the oral dosage regimen in pigs of this age range. The favourable pharmacokinetics of aditoprim in pigs (large apparent volume of distribution, long elimination half-life and high bioavailability) may permit introduction of this drug into swine practice, after safety and residue depletion studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01839185
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    Biovailability of ivermectin administered orally to dogs (1992)
    Springer
    Veterinary research communications 16 (1992), S. 125-130 
    Details
    ISSN: 1573-7446
    Keywords: bioavailability ; dogs ; ivermectin ; oral formulations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The bioavailability of three formulations of ivermectin was determined following oral administration to dogs. The average peak plasma level (C max) of ivermectin administered in the standard tablet formulation at 6 and 100 µg/kg of body weight was 2.97 and 44.31 ng/g, respectively. This suggest dose-dependent pharmacokinetics.C max and total ivermectin bioavailability, as assessed from the area under the plasma curve (AUC), were similar between two tablet formulations of ivermectin administered at 100 µg/kg. Furthermore,C max was similar following administration of radiolabelled ivermectin at 6 µg/kg in either a beef-based chewable formulation or in the standard tablet formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01839009
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  • 77
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    Pharmacokinetics following a single intravenous administration and a dosage regimen for sulfadoxine in buffalo calves (Bubalus bubalis) (1992)
    Springer
    Veterinary research communications 16 (1992), S. 215-219 
    Details
    ISSN: 1573-7446
    Keywords: pharmacokinetics ; dosage regimen ; sulfadoxine ; Bubalus bubalis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01839158
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  • 78
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    Interspecies differences in the pharmacokinetics of kanamycin and apramycin (1992)
    Springer
    Veterinary research communications 16 (1992), S. 293-300 
    Details
    ISSN: 1573-7446
    Keywords: apramycin ; blood ; chemotherapy ; chickens ; goats ; kanamycin ; pharmacokinetics ; pigeons ; rabbits ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Comparative studies on some selected pharmacokinetic parameters for kanamycin in sheep, goats, rabbits, chickens and pigeons, and for apramycin in sheep, rabbits, chickens and pigeons were carried out after intravenous administration of the two drugs at a dose of 10 mg/kg. The results revealed that a two-compartment open model was most suitable for kanamycin, while for apramycin a one-compartment open model was usually optimal. The log distribution rate constant (α) of kanamycin was significantly correlated to the log of the body mass (r=0.919,n=5,p〈0.05). Interspecies differences in the apparent volume of distribution (Vda) of kanamycin were small. These differences were larger for apramycin, as were the variations in the area under the serum concentration-time curve (AUC) and in the total body clearance (ClB) of both kanamycin and apramycin, both having almost a threefold difference depending on the species but without any correlation to body mass. The values of the log half-life of kanamycin in the mammals in this study and also those from data in the literature revealed a significant correlation with log body mass between animal species according to the equation: $$t_{{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}\beta } = 38.47W^{0.21} (r = 0.7648,n - 10,p〈 0.05)$$ .
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01839328
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  • 79
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    Algorithms to rapidly achieve and maintain stable drug concentrations at the site of drug effect with a computer-controlled infusion pump (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 147-169 
    Details
    ISSN: 1573-8744
    Keywords: computers ; pharmacokinetics ; pharmacodynamics ; infusions ; drug delivery ; computer driven ; effect site
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Computer-controlled infusion pumps incorporating an internal model of drug pharmacokinetics can rapidly achieve and maintain constant drug concentrations in the plasma. Although these pumps offer more accurate titration of intravenous drugs than is possible with simple boluses or constant rate infusions, the choice of the plasma as the target site is arbitrary. The plasma is not the site of drug effect for most drugs. This manuscript describes two algorithms for calculation of the infusion rates necessary for a computer-controlled infusion pump to rapidly achieve, and then maintain, the desired target concentration at the site of drug effect rather than in the plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01070999
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  • 80
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    Application of semilinear canonical correlation to the measurement of opioid drug effect (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 611-635 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; pharmacodynamics ; plasma concentration-effect relation-ship ; anesthesia ; analgesic ; narcotic ; opioids ; alfentanil ; brain ; electroencephalograph ; spectral edge ; semilinear canonical correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract To examine the relationship between the electroencephalograph (EEG) and plasma opioid concentration, one would like to collapse the high-dimensional EEG signal into a univariate quantity. Such a simplification of the EEG is desirable because a univariate quantity can be modeled using standard nonlinear regression techniques, and because most of the information in the EEG is redundant or unrelated to drug concentration. In previous studies of the EEG response to opioids, the manner in which a univariate component was extracted from the EEG was ad hoc.In this paper, this extraction was performed optimally using a new statistical technique, semilinear canonical correlation. Data from 15 patients who received an intravenous infusion of the semisynthetic opioid alfentanil were analyzed. The components of the EEG that were nearly maximally correlated with plasma drug concentration were found, based on a standard pharmacokinetic-pharmacodynamic model. Two new EEG components were produced from the powers in the frequency spectrum of the EEG: a weighted sum of the logarithms of the powers, and a weighted sum of the powers expressed as percentages of the total power. These components both had a median R2 of 0.84, compared to median R2sranging from 0.37 to 0.83 for five commonly used ad hocEEG components. The new components also had less variability in R2 between subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01064422
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  • 81
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    Building population pharmacokineticpharmacodynamic models. I. Models for covariate effects (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 511-528 
    Details
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; population analysis ; model building ; generalized additive models ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract One major task in clinical pharmacology is to determine the pharmacokinetic-pharmacodynamic (PK-PD) parameters of a drug in a patient population. NONMEM is a program commonly used to build population PK-PD models, that is, models that characterize the relationship between a patient's PK-PD parameters and other patient specific covariates such as the patient's (patho)physiological condition, concomitant drug therapy, etc. This paper extends a previously described approach to efficiently find the relationships between the PK-PD parameters and covariates. In a first step, individual estimates of the PK-PD parameters are obtained as empirical Bayes estimates, based on a prior NONMEM fit using no covariates. In a second step, the individual PK-PD parameter estimates are regressed on the covariates using a generalized additive model. In a third and final step, NONMEM is used to optimize and finalize the population model. Four real-data examples are used to demonstrate the effectiveness of the approach. The examples show that the generalized additive model for the individual parameter estimates is a good initial guess for the NONMEM population model. In all four examples, the approach successfully selects the most important covariates and their functional representation. The great advantage of this approach is speed. The time required to derive a population model is markedly reduced because the number of necessary NONMEM runs is reduced. Furthermore, the approach provides a nice graphical representation of the relationships between the PK-PD parameters and covariates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061469
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    A physiologically based pharmacokinetic model for nicotine and cotinine in man (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 591-609 
    Details
    ISSN: 1573-8744
    Keywords: nicotine ; cotinine ; pharmacokinetics ; physiologically-based pharmacokinetic model ; interindividual variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Physiologically based pharmacokinetic (PBPK) models have been developed describing the disposition kinetics of nicotine and its major metabolite, cotinine, in man. Separate 9-compartment, flow-limited PBPK models were initially created for nicotine and cotinine. The physiological basis for compartment designation and parameter selection has been provided;chemical-specific tissue-to-blood partition coefficients and elimination rates were derived from published human and animal data. The individual models were tested through simulations of published studies of nicotine and cotinine infusions in man using similar dosing protocols to those reported. Each model adequately predicted the time course of nicotine or cotinine concentrations in the blood and urine following the administration of nicotine or cotinine. These individual models were then linked through the liver compartments to form a nicotine-cotinine model capable of predicting the metabolic production and disposition of cotinine from administered nicotine. The potential for integrating this functional PBPK model with an appropriate pharmacodynamic model for the characterization of nicotine's physiological effects is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01064421
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    Neural networks in pharmacodynamic modeling. Is current modeling practice of complex kinetic systems at a dead end? (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 397-412 
    Details
    ISSN: 1573-8744
    Keywords: neural networks ; pharmacodynamics ; pharmacokinetics ; modeling ; drug effect prediction ; alfentanil ; model testing ; system analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Neural networks (NN) are computational systems implemented in software or hardware that attempt to simulate the neurological processing abilities of biological systems, in particular the brain. Computational NN are classified as parallel distributed processing systems that for many tasks are recognized to have superior processing capability to the classical sequential Von Neuman computer model. NN are recognized mainly in terms of their adaptive learning and selforganization features and their nonlinear processing capability and are considered most suitable to deal with complex multivariate systems that are poorly understood and difficult to model by classical inductive,logically structured modeling techniques. A NN is applied to demonstrate one of the potentially many applications of NN for modeling complex kinetic systems. The NN was used to predict the effect of alfentanil on the heart rate resulting from a complex infusion scheme applied to six rabbits. Drug input-drug effect data resulting from a repeated, triple infusion rate scheme lasting from 30 to 180 min was used to train the NN to recognize and emulate the input-effect behavior of the system. With the NN memory fixed from the 30- to 180-min learning phase the NN was then tested for its ability to predict the effect resulting from a multiple infusion rate scheme applied in the subsequent 180 to 300 min of the experiment. The NN's ability to emulate the system (30–180 min) was excellent and its predictive extrapolation capability (180–300 min) was very good (mean relative prediction accuracy of 78%). The NN was best in predicting the higher intensity effect and was able to identify and predict an overshoot phenomenon likely caused by a withdrawal effect from acute tolerance. Current modeling philosophy and practice is discussed on the basis of the alternative offered by NN in the modeling of complex kinetic systems. In modeling such systems it is questioned whether traditional modeling practice that insists on structure relevance and conceptually pleasing structures has any practical advantages over the empirical NN approach that largely ignores structure relevance but concentrates on the emulation of the behaviorof the kinetic system. The traditional searching for appropriate models of complex kinetic systems is a painstakingly slow process. In contrast, the search for empirical models using NN will continue to improve, limited only by technological advances supporting the very promising NN developments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062465
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  • 84
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    Application of cladistics to the analysis of genotype-phenotype relationships (1992)
    Springer
    European journal of epidemiology 8 (1992), S. 3-9 
    Details
    ISSN: 1573-7284
    Keywords: Atherosclerosis ; Cladistics ; Genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We seek to understand the relative contribution of allelic variations of a particular gene to the determination of an individual's risk of atherosclerosis or hypertension. Work in progress is focusing on the identification and characterization of mutations in candidate genes that are known to be involved in determining the phenotypic expression of intermediate biochemical and physiological traits that are in the pathway of causation between genetic variation and variation in risk of disease. The statistical strategy described in this paper is designed to aid geneticists and molecular biologists in their search to find the DNA sequences responsible for the genetic component of variation in these traits. With this information we will have a more complete understanding of the nature of the organization of the genetic variation responsible for quantitative variation in risk of disease. It will then be possible to fully evaluate the utility of measured genetic information in predicting the risk of common diseases having a complex multifactorial etiology, such as atherosclerosis and hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00145343
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    Hemodynamic and antiischemic effects of tedisamil in humans (1992)
    Springer
    Cardiovascular drugs and therapy 6 (1992), S. 353-360 
    Details
    ISSN: 1573-7241
    Keywords: tedisamil ; coronary artery disease ; hemodynamics ; right heart catheterization ; catecholamines ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p〈.01), and 9.2 beats/min (p〈.001); exercise: 6, 4.6, and 8.9 beats/min (p〈.01), respectively] and the index of myocardial oxygen consumption (exercise: 6–9% in each group) associated with an improvement of ST-segment depression [−12.1%, −10.7%, −41.9% (p〉.01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p〈.05), respectively] and during exercise (2–8%), being significant only at rest in the highest dose group, stroke volume remained unaltered. Pulmonary artery pressure, pulmonary capillary wedge pressure, right-ventricular ejection fraction, and pulmonary vascular resistance were without significant changes. Blood pressure and systemic vascular resistance tended to increase, associated with a decrease in plasma catecholamines (20–40%). Tedisamil produced a dose-dependent prolongation of QTc duration [+2%, +6%, +12% (p〈.05), respectively] with PQ and QRS unaltered. The elimination half-life of tedisamil IV ranges between 6.8 and 7.8 hours. In conclusion, tedisamil, at a dose of 0.3 mg/kg IV, was well tolerated and was found to have favorable hemodynamic and antiischemic effects in patients with ischemic heart disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00051021
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    Abnormal craniofacial development in cyclopic salmonid fishes (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 23-29 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Different types and degrees of “spontaneous” and artificially induced cyclopic malformation in fishes are defined. Symmetrical cyclopia ranges from approximation of the eyes, to partial merger of the eyes in the midline, to complete cyclopia with a single median eye. It is always associated with dorsal displacement of the rostral-nasal apparatus to the top of the head. Skeletal reorganization associated with symmetrical cyclopia is described for the first time, using hatchery material of Salmo gairdneri and S. trutta. Development of the nasal capsule is essentially normal, except for position; the trabeculae cranii remain in the normal position but show modified shape corresponding to the degree of cyclopia. The jaw apparatus is modified through anterior foreshortening, especially the upper jaws. The branchial apparatus is unaffected. The condition demonstrates that later morphogenesis of the nasal capsule and trabeculae cranii are independent of each other. Cyclopia appears to result from alteration of relative position and timing in developmental events in the head, especially the prosencephalon.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110104
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    Interrenal of a female gymnophione amphibian, Ichthyophis beddomei, during the annual reproductive cycle (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 201-206 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The interrenal (adrenal) of Ichthyophis beddomei lies on the ventral side of the kidney, distributed in four zones. It is separated from the renal tissue by a thin layer of connective tissue and contains both adrenocortical and chromaffin cells. Adrenocortical tissue constitutes a major portion of the interrenal islets; the chromaffin tissue consists of a few cells located at the peripheries of the interrenal islets. Histochemical studies demonstrate the presence of Δ53β-hydroxysteroid dehydrogenase, 17 β-hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and sudanophilic lipids in the adrenocortical tissue, suggesting its steroidogenic potential. Annual histometric and histochemical studies show two peaks of interrenal activity: (1) during the breeding phase of the reproductive cycle (January and February) and (2) during the season of heavy monsoon rains (June and July) in the postbreeding phase.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110208
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110301
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  • 89
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    Functional osteology of the avian wrist and the evolution of flapping flight (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 259-268 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The avian wrist is extraordinarily adapted for flight. Its intricate osteology is constructed to perform four very different, but extremely important, flight-related functions. (1) Throughout the downstroke, the cuneiform transmits force from the carpometacarpus to the ulna and prevents the manus from hyperpronating. (2) While gliding or maneuvering, the scapholunar interlocks with the carpometacarpus and prevents the manus from supinating. By employing both carpal bones simultaneously birds can lock the manus into place during flight. (3) Throughout the downstroke-upstroke transition, the articular ridge on the distal extremity of the ulna, in conjuction with the cuneiform, guides the manus from the plane of the wing toward the body. (4) During take-off or landing, the upstroke of some heavy birds exhibits a pronounced flick of the manus. The backward component of this flick is produced by reversing the wrist mechanism that enables the manus to rotate toward the body during the early upstroke. The upward component of the flick is generated by mechanical interplay between the ventral ramus of the cuneiform, the ventral ridge of the carpometacarpus, and the ulnocarpo-metacarpal ligament.Without the highly specialized osteology of the wrist it is doubtful that birds would be able to carry out successfully the wing motions associated with flapping flight. Yet in Archaeopteryx, the wrist displays a very different morphology that lacks all the key features found in the modern avian wrist. Therefore, Archaeopteryx was probably incapable of executing the kinematics of modern avian powered flight.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110303
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    Histology, histochemistry, and ultrastructure of the harderian gland of the snake Coluber viridiflavus (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 207-212 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Analyses of the histology, histochemistry, and ultrastructre of the Harderian gland of Coluber viridiflavus prove the gland to be compound acinar and to produce a seromucous secretion. Acinar cells (type I) contain secretory granules that are composite, consisting ultrastructurally of three distinct parts that are sharply separated. They are similar to the “special secretory granules” described in the cells of the Harderian gland of the lizard Podarcis s. sicula. Some acini of the most anterior and posterior parts of the gland are mucous. Acinar cells (type II) of this type contain secretory granules that are Alcian blue/PAS positve. At the ultrastructural level, they appear homogeneous and of low density, characteristic of mucous secretions. These mucus-secreting anterior and posterior parts of the Harderian gland may by considered as regions of intial differentiation of the anterior and posterior lacrimal galnds.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110209
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  • 91
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    Development of the subdigital adhesive pads of Ptyodactylus guttatus (Reptilia: Gekkonidae) (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 243-258 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Subdigital adhesive pads play an important role in the locomotion of many species of gekkonid lizards. These pads consist of integrated components derived from the epidermis, dermis, vascular system, subcuticular tendons, and phalanges. These components become intimately associated with each other during the developmental differentiation of the digits and the sequence of this integration is outlined herein in Ptyodactylus guttatus. The pads initially appear as paired swellings at the distal tips of the digits. Subsequently, a fan-like array of naked scansors develops on the ventral surface of each digit, at about the same time that scales differentiate over the surface of the foot as a whole. At the time of appearance of the naked scansors, the vascular sinus system of the pad also differentiates, along with subcuticular connective tissue specializations. At this stage the digits, along with the rest of the body, are clad in an embryonic periderm. Only after hatching and as the periderm is shed, do the epidermal setae and spines appear. The developmental sequence described here is consistent with predictions previously advanced about the evolutionary origin and elaboration of subdigital pads in gekkonid lizards. The paucity of available staged embryonic material leaves many questions unresolved.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110302
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  • 92
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    Histological, histochemical, and biochemical changes in the annual oviduct cycle of the agamid, Calotes versicolor (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 211 (1992), S. 295-306 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Histology, histochemistry, and biochemistry of the oviduct change seasonally in relationship to the annual ovarian cycle of Calotes versicolor. Histological changes show distinct changes in various components of the infundibulum, uterus and vagina of the oviduct. The active phase in the oviduct cycle of C. versicolor is relatively long, extending from April to October. Histochemical results of the oviduct during the breeding season show PAS-positive glycosaminoglycans in the mucosal epithelium as well as the presence of hydroxysteroid dehydrogenases, esterase, and intense acid phosphatase activity in the uterine glands. Biochemically alkaline and acid phosphatase show marked cyclic changes in the infundibulum and uterus respectively during the oviduct cycle. Greater activity was observed during the breeding season. β-Glucuronidase, on the other hand, shows an inverse relationship with the oviduct cycle being most active during the regressive phase and least at the time of reproductive phase.
    Additional Material: 23 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052110307
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  • 93
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120101
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  • 94
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    Patterns of peripheral innervation of the tongue and hyobranchial apparatus in caecilians (Amphibia: Gymnophiona) (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 37-53 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The innervation of the musculature of the tongue and the hyobranchial apparatus of caecilians has long been assumed to be simple and to exhibit little interspecific variation. A study of 14 genera representing all six families of caecilians demonstrates that general patterns of innervations by the trigeminal, facial, glossopharyngeal, and vagus nerves are similar across taxa but that the composition of the “hypoglossal” nerve is highly variable. Probably in all caecilians, spinal nerves 1 and 2 contribute to the hypoglossal. In addition, in certain taxa, an “occipital,” the vagus, and/or spinal 3 appear to contribute fibers to the composition of the hypoglossal nerve. These patterns, the lengths of fusion of the contributing elements, and the branching patterns of the hypoglossal are assessed according to the currently accepted hypothesis of phylogenetic relationships of caecilians, and of amphibians. An hypothesis is proposed that limblessness and a simple tongue, with concomitant reduced complexity of innervation of muscles associated with limbs and the tongue, has released a constraint on pattern of innervation. As a consequence, a greater diversity and, in several taxa, greater complexity of neuroanatomical associations of nerve roots to form the hypoglossal are expressed.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052120105
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  • 95
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    Electronic Resource
    Functional stages in the interrenal cells of Rana perezi (Anura: Ranidae) (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 65-70 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The electron density of the lipid droplets and mitochondrial matrix of the interrenal cells of Rana perezi differs during the year. This makes it possible to characterize the different stages of interrenal cell activity. A droplet/mitochondria index, based on their relative size, may provide an indicator of cellular activity.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120107
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  • 96
    Electronic Resource
    Electronic Resource
    Development and differentiation of the eye in Platynereis dumerilii (Annelida, Polychaeta) (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 71-85 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The nereid polychaete, Platynereis dumerilii, possess two pairs of post-trochophoral eyes with one vitreous body each. The development of these eyes has first been observed in 2-day-old larvae. Whether the eye anlagen arise from stem cells or from undifferentiated ectodermal tissue was not determined. At first, the anlagen of the anterior and the posterior eyes adjoin each other. They separate in late 3-day-old larvae. The first separated eye complexes consist each of two supporting and two sensory cells. The supporting cells synthesize two different kinds of granules, the pigment granules of the pigment cup and the prospective tubules of the vitreous body. These tubules accumulate in the distal process of the supporting cell. The vitreous body is formed by compartments of the supporting cells filled with the osmiophilic vitreous body tubules. The short, bulbar photosensory processes bear microvilli that emerge into the ocular cavity. At the apex of each sensory cell process, a single cilium (or occasionally two) arises. The sensory cells contain a different kind of pigment granule within their necks at the level of the pigment cup. The rate of eye development and differentiation varies. New supporting cells are added to the rim of the eye cup. They contribute to the periphery of the vitreous body like onion skins, and sensory cells move between supporting cells. The older the individual compartments of the vitreous body are, the more densely packed is their content of vitreous body tubules. Elongation of the sensory and supporting cell processes of the older cells increases the volume of the eye. The eyespots of the trochophore are briefly described as of the two-celled rhabdomeric type with a single basal body with ciliary rootlet.
    Additional Material: 20 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120108
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  • 97
    Electronic Resource
    Electronic Resource
    Kinematics of the jaw and hyolingual apparatus during feeding in Caiman crocodilus (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 141-154 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Movements of the neck, jaws, and hyolingual apparatus during inertial feeding in Caiman crocodilus were studied by cineradiography. Analysis reveals two kinds of cycles: inertial bites (reposition, kill/crush, and transport) and swallowing cycles. They differ in their gape profile and in displacement of the neck, cranium, and hyolingual apparatus.Inertial bites are initiated by an elevation of the neck and cranium; the head is then retracted backward, the prey simultaneously being lifted by the hyolingual apparatus. Next the lower jaw is depressed, and the prey is rapidly pushed further upward by the hyolingual apparatus. Thereafter fast mouth-closure occurs with the neck and cranium being abruptly depressed, the lower jaw elevated, and the hyolingual apparatus rapidly retracted ventrally. Depression of the neck and cranium thrusts the head forward and impacts the backward moving prey more posteriorly in the oral cavity.Swallowing cycles initially involve movement of the hyoid in front of the prey followed by rapid posteroventrad retraction of the hyoid, forcing the prey into the esophagus during opening and closing of the mouth. After mouth-closure, the hyoid apparatus is again protracted.Jaws, neck, tongue, and hyoid apparatus play an active role during intertial feeding sequences. At the beginning of a feeding sequence, the hyolingual apparatus mainly moves dorsoventrally, whereas toward the end of a sequence anteroposterior displacements of the hyoid are prominent. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120205
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  • 98
    Electronic Resource
    Electronic Resource
    Morphology of the reproductive tract in a lizard exhibiting incipient viviparity (Sphenomorphus fragilis) and its implications for the evolution of the reptilian placenta (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 163-173 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology of the female reproductive tract and corpus luteum is examined in Sphenomorphus fragilis, a lizard from the lowland regions of New Guinea exhibiting incipient viviparity. Females oviposit eggs that hatch either immediately or within a few hours. Corpora lutea form from ovulated follicles and decrease in diameter as embryonic development progresses. The oviduct from vitellogenic females is sparsely populated with well developed uterine glands containing secretory granules. The eggs are covered with a relatively thin shell (10 μm thick) composed of an inner boundary layer and proteinacous fibers. The secreted shell is complete by early neurulation. Shell morphology does not change throughout the remainder of the in utero incubation period. A well vascularized uterus and chorioallantoic membrane provide simple placentation. These findings suggest that the reduction in shell thickness associated with the evolution of a placenta is due to a decrease in the number of shell glands in the uterus and is not a delay or inhibition of the shelling process per se. This hypothesis further suggests that the selective forces favoring shell gland loss act on the vitellogenic female during gland recruitment which occurs prior to ovulation and not on the pregnant female. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120207
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  • 99
    Electronic Resource
    Electronic Resource
    Histology of the esophagus of the adult frog Rana perezi (Anura: Ranidae) (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 191-200 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Study of the esophageal microscopic morphology of adult Rana perezi by light and electron microscopy discloses some large folds throughout the esophagus that are in themselves ringed. Glandular ostia open in the furrows of the luminal surface. The esophageal wall is made up of a connective adventitia rich in melanocytes, a muscular tunica, a connective and glandular subepithelial layer, and a pseudostratified ciliated epithelium. This epithelium basically consists of ciliated, goblet, basal, microvillous-apex, and migratory cells. Two types of goblet cells are distinguished with regard to the granular ultrastructure. The microvillous-apex cell has not been found in other amphibians. It shows a very differentiated morphology with a high number of mitochondria. The basal cells give the epithelium a pseudostratified morphology, and they have a proliferative function. Glands are branched and drain through an excretory duct that has a monolayered mucosecreting epithelium. The glandular units are formed by two principal types of cells: mucosecretory and serous. © 1992 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120302
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  • 100
    Electronic Resource
    Electronic Resource
    Spermiophagy by the spermathecal epithelium of the salamander Eurycea cirrigera (1992)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 212 (1992), S. 281-290 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The spermathecae of Eurycea cirrigera are exocrine glands in the cloaca that secrete a substance that bathes sperm stored in the lumen after mating and prior to oviposition. Many sperm remain in the spermathecae after oviposition, and the spermathecal epithelium becomes spermiophagic. Pseudopodia enclose sperm into endocytic vacuoles. The vacuoles become associated with primary lysosomes in the cytoplasm. Following formation of secondary lysosomes and resulting condensation of the sperm fragments, residual bodies are exocytized into the surrounding connective tissue stroma. By the start of the next breeding cycle, most sperm remaining from the previous mating have been degraded, but some sperm remain in the lumen, and the viability of these sperm is unknown. © 1992 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052120307
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