Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism
Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism
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DOI：
10.1007/s10038-008-0324-9
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发表时间：
2008-07
影响因子：
3.5
通讯作者：
S. Suwannakul;I. Ieiri;M. Kimura;K. Kawabata;H. Kusuhara;Takeshi Hirota;S. Irie;Y. Sugiyama;S. Higuchi
中科院分区：
文献类型：
--
作者：
S. Suwannakul;I. Ieiri;M. Kimura;K. Kawabata;H. Kusuhara;Takeshi Hirota;S. Irie;Y. Sugiyama;S. Higuchi
研究SLCO1B1多态性对奥美沙坦药代动力学及普伐他汀与奥美沙坦药代动力学相互作用的影响。第1天，10名健康志愿者口服普伐他汀（10mg）。3天洗脱期后，每名受试者接受奥美沙坦美多索米（10mg）治疗3天。第8天，患者同时服用奥美沙坦美多索米（10mg）和普伐他汀（10mg），比较SLCO1B1基因型（* 1b/* 1b、* 1b/* 15和* 15/* 15）与各单剂量期的药代动力学特征。在单剂量期，奥美沙坦在* 15/* 15组的平均cmax和AUC 0-24倾向于高于* 1b/* 1b组，而在* 15/* 15组的平均CL t/F（±SD）显著低于* 1b/* 1b组。普伐他汀和RMS-416单给药期和共给药期的任何药代动力学参数均无统计学差异。这些结果表明OATP1B1在奥美沙坦的药代动力学中起作用，同时服用奥美沙坦并不影响普伐他汀及其代谢物RMS-416的药代动力学，尽管由于本研究样本量小，需要更大规模的临床研究来证实这些观察结果。
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.