期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 62, 期 6, 页码 682-689出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2125.2006.02706.x
关键词
CYP2C8 polymorphisms; drug interaction; fluvoxamine; pharmacokinetics; rosiglitazone
Aims. To determine the effect of CYP2C8 genotype and of fluvoxamine on the pharmacokinetics of rosiglitazone. Methods. Twenty-three healthy subjects with the following genotypes were included in a two-phase, open-label, cross-over trial: CYP2C8*3/*3 (n = 3), CYP2C8*1/*3 (n = 10) and CYP2C8*1/*1 ( n = 10). In Phase A, the subjects were given 4 mg rosiglitazone as a single oral dose. In Phase B, the subjects were treated with multiple oral doses of 50 mg fluvoxamine maleate for 3 days prior to the single oral administration of 4 mg rosiglitazone. Plasma concentrations of rosiglitazone and relative amounts of N-desmethylrosiglitazone were measured in both phases for 24 h after drug administration. Results. The pharmacokinetics of rosiglitazone and N-desmethylrosiglitazone were not significantly different between the CYP2C8 genotypic groups. Fluvoxamine caused a statistically significant (P = 0.0066) increase in the AUC(0-infinity) of rosiglitazone, with a geometric mean ratio of 1.21 [95% confidence interval (CI) 1.06 - 1.39]. The elimination half-life (t(1/2)) was also significantly higher (P = 0.0203) with a geometric mean ratio of 1.38 [95% CI 1.06 - 1.79]. The coadministration of fluvoxamine had no influence on the pharmacokinetics of N-desmethylrosiglitazone. Conclusion. The importance of the CYP2C8*3 mutation in the in vivo metabolism of rosiglitazone could not be confirmed. Fluvoxamine increased the AUC(0-infinity) and t(1/2) of rosiglitazone moderately and hence may be a weak inhibitor of CYP2C8.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据