Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects
Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects
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DOI：
10.1007/s00228-009-0625-8
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发表时间：
2009-06-01
影响因子：
2.9
通讯作者：
Furuta, Takahisa
中科院分区：
文献类型：
--
作者：
Kodaira, Chise;Sugimoto, Mitsushige;Furuta, Takahisa
背景和目的多药耐药转运蛋白基因1（MDR 1）对几种底物的生物利用度和动力学的影响尚未完全阐明。方法15名健康志愿者，均为CYP 2C 19快快代谢型，随机分为3组：C/C（n=5）、C/T（n=5）和T/T（n=5）。兰索拉唑30 mg口服给药15天。在第1天和第15天测定胃内pH值和血浆兰索拉唑水平。结果第1天，T/T组兰索拉唑平均Cmax显著高于C/C组和C/T组（T/T1，248，C/C618，C/T607 ng/ml; P=0.038）。在第15天，兰索拉唑的Cmax观察到相似的MDR 1基因型依赖性差异，尽管小于第1天观察到的差异。与此相反，兰索拉唑给药后第1天和第15天的胃内pH值在MDR 1基因型组之间没有差异。结论虽然样本量较小，但我们的研究表明MDR 1 C3435 T多态性影响药代动力学，但不影响药效学（即，胃内pH），兰索拉唑在CYP 2C 19快速代谢者中的作用。
Background and aims The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects.Methods Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n=5), C/T (n=5), and T/T (n=5). Lansoprazole 30 mg was administered orally for 15 days. The intragastric pH and plasma lansoprazole levels were determined on days 1 and 15. Results On day 1, the mean C-max of lansoprazole in the T/T group was significantly higher than that in the C/C or C/T groups (T/T1,248, C/C618, C/T607 ng/ml; P=0.038). On day 15, similar MDR1 genotype-dependent differences were observed in the Cmax of lansoprazole, although smaller than the differences observed on day 1. In contrast, the intragastric pH attained after lansoprazole administration did not differ among MDR1 genotype groups on either day 1 or day 15.Conclusion Although the sample size was small, our study demonstrated that the MDR1 C3435T polymorphism influenced the pharmacokinetics, but not the pharmacodynamics (i.e., intragastric pH), of lansoprazole in rapid metabolizers of CYP2C19.