title: CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers.
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.
authors.affiliation: Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukuda
authors.forename: S
authors.initials: S
authors.lastname: Onishi
authors.forename: S
authors.initials: S
authors.lastname: Fukuen
authors.forename: Y
authors.initials: Y
authors.lastname: Ikenaga
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Maihara
authors.forename: K
authors.initials: K
authors.lastname: Momiyama
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Fujio
authors.forename: J
authors.initials: J
authors.lastname: Azuma
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000097:blood* / Q000494:pharmacology
chemical_list: D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009543:Nifedipine