CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers.
CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers.
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DOI：
10.1038/sj.tpj.6500218
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Azuma, J.
中科院分区：
文献类型：
--
作者：
Fukuda, T.;Onishi, S.;Azuma, J.
CYP 3A 5的表达受单核苷酸多态性（SNP）的调节。CYP 3A 5基因型可能导致CYP 3A介导的药物代谢的显著个体间差异。硝苯地平是CYP 3A 4和CYP 3A 5的典型体外底物。本研究的目的是阐明CYP 3A 5基因型对健康受试者硝苯地平处置的影响。16例日本健康男性受试者（8例受试者：CYP 3A 5 *1/*3; 8例受试者：CYP 3A 5 *3/*3）接受含10 mg硝苯地平的单粒胶囊给药。采集血标本分析硝苯地平及其代谢产物M-1的药代动力学。硝苯地平的血药浓度-时间曲线下面积（AUC）、血药峰浓度（Cmax）和终末半衰期（t1/2）以及硝苯地平AUC与M-1 AUC的比值显示出较大的组内变异性，但两种基因型之间无显著差异。基于目前的研究结果，CYP 3A 5基因多态性的功能相关性应在临床试验中重新评估。
CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5*1/*3; eight subjects: CYP3A5*3/*3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-l). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (Cmax) and the terminal half-life (t1/2) of nifedipine, and the ratio of the nifedipine AUC to M-l AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials.