期刊
DRUG METABOLISM AND PHARMACOKINETICS
卷 22, 期 5, 页码 358-366出版社
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.22.358
关键词
aripiprazole; antipsychotics; pharmacokinetics; CYP2D6 genotypes; CYP2D6*41
We investigated the pharmacokinetics (PK) of aripiprazole, a newly developed antipsychotic, and its active metabolite in healthy Japanese, and the influence of CYP2D6 polymorphism on the PK of aripiprazole. Following a single oral 6 mg dose, the mean C-max, t(max), and t(1/2,z) (terminal phase half life) of aripiprazole were 31.0 ng/mL, 3.6 hr, and 61.0 hr, respectively. The t(1/2,z) in CYP2D6 IM subjects (75.2 hr) was significantly (p < 0.01) longer than that in CYP2D6 EM subjects (45.8 hr), and the systemic clearance of IM subjects was approximately 60% that of EM subjects. The PK in one subject with the CYP2D6* 41 homozygote was similar to that of IM subjects. In repeated oral administration, plasma concentrations of aripiprazole and active metabolite both reached a steady state by Day 14. The half-life of aripiprazole following repeated administration was similar to that following single administration, suggesting that pharmacokinetics was constant during 14-day administration. Our investigations revealed that there is no clear ethnic difference between Japanese and Western subjects in terms of mean plasma PK, while the CYP2D6* 10 allele distinctive to Asian populations influences the PK of aripiprazole. Moreover, our observations suggest that the CYP2D6* 41 allele significantly affects drug-metabolizing activity.
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