1. ¹Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan
2. ²Japan Clinical Laboratories, Inc., Bioassay Division, Japan
3. ³Osaka Pharmacology Research Clinic, Japan

Correspondence: J Azuma, Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel: +81 6 6879 8258; Fax: +81 6 6879 8259; E-mail: azuma@phs.osaka-u.ac.jp

⁴These two authors contributed equally to this work

Received 18 February 2003; Revised 6 October 2003; Accepted 14 October 2003; Published online 2 December 2003.

Abstract

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.