期刊
JOURNAL OF HUMAN GENETICS
卷 53, 期 10, 页码 899-904出版社
NATURE PUBLISHING GROUP
DOI: 10.1007/s10038-008-0324-9
关键词
olmesartan; pravastatin; pharmacokinetics; interaction; OATP1B1; SLCO1B1; polymorphisms
资金
- Health and Labor Sciences Research
- Ministry of Health, Labor and Welfare, Tokyo, Japan
The impact of SLCO1B1 polymorphism on the pharmacokinetics of olmesartan and on the pharmacokinetic interaction between pravastatin and olmesartan was investigated. On day 1, ten healthy volunteers took an oral dose (10 mg) of pravastatin. After a 3-day washout period, each subject received olmesartan medoxomil (10 mg) for 3 days. On day 8, they received olmesartan medoxomil (10 mg) and pravastatin (10 mg) concurrently, and pharmacokinetic profiles were compared with those in each single-dose phase with regard to the SLCO1B1 genotypes (*1b/*1b, *1b/*15, and *15/*15). In the single-dose phase, the mean C(max) and AUC(0-24) of olmesartan tended to be higher in *15/*15 subjects than in *1b/*1b subjects, while the mean CL(t)/F (+/- SD) in *15/*15 subjects was significantly lower than that in *1b/*1b subjects. No statistically significant differences were observed in any pharmacokinetic parameters between single-dose and co-administration phases for both pravastatin and RMS-416. These results suggest that OATP1B1 plays a role in the pharmacokinetics of olmesartan, and the co-administration of olmesartan does not affect the pharmacokinetics of pravastatin or its metabolite, RMS-416, although larger scale clinical studies are needed to confirm these observations due to the small sample size in the present study.
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