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  • 1
    Electronic Resource
    Electronic Resource
    CYP2C19 polymorphism effect on phenobarbitone (2000)
    Springer
    European journal of clinical pharmacology 55 (2000), S. 821-825 
    Details
    ISSN: 1432-1041
    Keywords: Key words Phenobarbitone ; CYP2C19 ; Genetic polymorphism ; Pharmacokinetics ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. Methods: A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. Results: Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. Conclusion: In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050703
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  • 2
    Electronic Resource
    Electronic Resource
    No evidence of association between apolipoprotein E gene regulatory region polymorphism and Alzheimer's disease in Japanese (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 1449-1456 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Apolipoprotein E ; gene ; promoter ; polymorphism ; Alzheimer's disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The reported association between −491 A/T polymorphism in the regulatory region of the apolipoprotein E gene (APOE) and increased risk for Alzheimer's disease (AD) is controversial: Studies of different racial and ethnic populations have found both positive and negative associations. Examination of −491 A/T polymorphism in 216 patients with sporadic AD and 157 age- and gender-matched controls from the Japanese population revealed that, in contrast to findings for Caucasian populations, the −491 T allele, but not the A allele, was significantly more prevalent in patients with AD than in controls. This difference disappeared when the subjects were stratified by the gene dose of the APOE ε4 allele. Moreover, logistic regression analysis, controlling for age, sex, and the presence of the APOE ε4 allele, showed no association between the −491 polymorphism and AD. These results suggest that −491 polymorphism does not independently confer susceptibility to AD, but that this polymorphism is in partial linkage disequilibrium with the APOE ε2/3/4 polymorphism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070008
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  • 3
    Electronic Resource
    Electronic Resource
    Autonomous Tool Path Generation in Robotic Polishing of an Aluminum Alloy (2003)
    s.l. ; Stafa-Zurich, Switzerland
    Key engineering materials Vol. 238-239 (Apr. 2003), p. 263-270 
    Details
    ISSN: 1013-9826
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
    URL: http://www.tib-hannover.de/fulltexts/2011/0528/01/46/transtech_doi~10.4028%252Fwww.scientific.net%252FKEM.238-239.263.pdf
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  • 4
    Electronic Resource
    Electronic Resource
    Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9 * 3 allele (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 65-68 
    Details
    ISSN: 1432-1041
    Keywords: Key words CYP2C9 ; Genetic polymorphism ; Diclofenac
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. Methods: A single dose of diclofenac was administered orally to 12 healthy subjects in whom the genotype of CYP2C9 had been determined previously. The disposition kinetics of diclofenac were compared between homozygotes for the wild type (CYP2C9*1/*1, n=6) and heterozygotes for the Leu359 variant (CYP2C9*1/*3, n=6). Results: For diclofenac, the following kinetic parameters were observed in the CYP2C9*1/*1 and CYP2C9*1/*3 subjects, respectively (mean ± SD): apparent oral clearance (ml/kg/h) 355.8 ± 56.9 and 484.4 ± 155.3; area under plasma concentration–time curve (μg h/ml) 2.7 ± 0.7 and 1.9 ± 0.6. The formation clearance of 4′-hydroxydiclofenac (ml/kg/h) was 63.6 ± 19.1 in the CYP2C9*1/*1 subjects compared with 75.9 ± 27.6 in the CYP2C9*1/*3 subjects. There were no significant differences in any of the kinetic parameters for either diclofenac disposition or formation clearance of 4′-hydroxydiclofenac between the two genotype groups. Conclusion: Since the disposition kinetics of diclofenac does not change in subjects with the single CYP2C9*3 mutant allele, it is suggested that the effects of CYP2C9 polymorphisms on the drug metabolism tend to be substrate specific.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050722
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