CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers

• DOI: 10.1038/sj.tpj.6500218
• Publication Date: 2003-12-02T12:03:48Z
• Authors: T Fukuda; S Onishi; S Fukuen; Y Ikenaga; M Ohno; K Hoshino; K Matsumoto; A Maihara; K Momiyama; T Ito; Y Fujio; J Azuma
• Keywords: Adult; Male; Analysis of Variance; Genotype; Nifedipine; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cytochrome P-450 Enzyme System; Area Under Curve; Cytochrome P-450 CYP3A; Humans; Female

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-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C(max)) and the terminal half-life (t(1/2)) of nifedipine, and the ratio of the nifedipine AUC to M-I 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.