Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism.
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.
Suwannakul
Suttasinee
S
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Ieiri
Ichiro
I
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. ieiri-ttr@umin.ac.jp.
Kimura
Miyuki
M
Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
Kawabata
Kiyoshi
K
Daiichi-Sankyo RD Associe Co., Ltd, Tokyo, Japan.
Kusuhara
Hiroyuki
H
Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Hirota
Takeshi
T
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Irie
Shin
S
Kyushu Clinical Pharmacology Research Clinic, Fukuoka, Japan.
Sugiyama
Yuichi
Y
Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Higuchi
Shun
S
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004347:Drug Interactions / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D000068557:Olmesartan Medoxomil; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017035:Pravastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D007093:Imidazoles; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D017035:Pravastatin