CYP2C192/3基因多态性和MDR1 C3435T对健康中国受试者中兰索拉唑药代动力学的影响。

Effects of genetic polymorphisms of CYP2C192/3 and MDR1 C3435T on the pharmacokinetics of lansoprazole in healthy Chinese subjects.

作者信息

Zhang Yu-Xin, Wei Shi-Jie, Yang Xiao-Ying, Zhang Wen-Ping, Wang Xin-Yu, Dang Hong-Wan

出版信息

Int J Clin Pharmacol Ther. 2014 Oct;52(10):850-5. doi: 10.5414/CP202059.

DOI:10.5414/CP202059

PMID:25109411

Abstract

OBJECTIVES

To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects.

METHODS

All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism.

RESULTS

Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05).

CONCLUSION

CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

摘要

目的

评估CYP2C19*2/*3和MDR1 C3435T基因多态性对健康中国受试者中兰索拉唑（LPZ）药代动力学的影响。

方法

所有24名受试者均来自一项生物等效性研究。采用液相色谱/质谱法测定LPZ的血浆浓度。通过聚合酶链反应-限制性片段长度多态性对受试者的细胞色素P450（CYP）2C19*2/*3和多药耐药转运蛋白基因1（MDR1）C3435T进行基因分型。

结果

CYP2C19广泛代谢者与中间代谢者之间，LPZ的给药前至T时间的浓度-时间曲线下面积（AUC(0-T)）、给药前至无穷大的浓度-时间曲线下面积（AUC(0-∞)）、t(1/2)以及表观口服清除率（CL/F）存在显著差异（p<0.05）。MDR1 C3435T基因多态性为C/C、C/T和T/T的受试者之间，LPZ的AUC(0-T)、AUC(0-∞)、最大血浆浓度和CL/F存在显著差异（p<0.05）。