No effect of MDR1 C3435T polymorphism on oral pharmacokinetics of telmisartan in 19 healthy Chinese male subjects
No effect of MDR1 C3435T polymorphism on oral pharmacokinetics of telmisartan in 19 healthy Chinese male subjects
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MDR1 C3435T 多态性对 19 名中国健康男性受试者替米沙坦口服药代动力学无影响
DOI：
10.1515/cclm.2009.019
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发表时间：
2009-01-01
影响因子：
6.8
通讯作者：
Li, Yuan-Jian
中科院分区：
文献类型：
--
作者：
Guo, Xin;Chen, Xiao-Ping;Li, Yuan-Jian
背景：已经确定替米沙坦在药物反应和药代动力学方面存在相当大的个体差异。本研究旨在探讨MDR1 C3435T多态性对替米沙坦单次口服后药代动力学的影响。方法：采用聚合酶链反应-限制性片段长度多态性方法对61例无亲缘关系男性志愿者进行MDR1 C3435T多态性基因分型。随机选择6个3435CC纯合子、8个3435CT杂合子和5个3435TT纯合子，接受单次口服40mg替米沙坦。用高效液相色谱-质谱法测定替米沙坦给药后48 h的血浆浓度。结果：替米沙坦tmax、Cmax、t1/2、AUC0 - 48、AUC0 -∞和清除率（CL）的个体间差异分别约为6倍、33倍、16倍、17倍、20倍和20倍。替米沙坦的Cmax （p=0.010）、t1/2 （p=0.029）和CL （p=0.010）均非正态分布。MDR1 3435TT纯合子的Cmax、tmax、t1/2、AUC0 - 48和AUC0 -∞似乎有所增加。而Cmax、tmax、t1/2、AUC0 - 48、AUC0 -∞、CL在MDR1 C3435T基因型间无显著差异。结论：MDR1 C3435T多态性不影响替米沙坦口服药代动力学。中华临床医学杂志2009；47:38-43。
Abstract Background: Considerable interindividual differences in both drug response and pharmacokinetics of telmisartan have been identified. This study was designed to investigate the influence of MDR1 C3435T polymorphism on pharmacokinetics of telmisartan after a single oral dose in healthy Chinese volunteers. Methods: A total of 61 unrelated male volunteers were genotyped for MDR1 C3435T polymorphism by using the polymerase chain reaction-restriction fragment length polymorphism method. Six 3435CC homozygotes, eight 3435CT heterozygotes, and five 3435TT homozygotes were randomly selected and received a single oral dose of 40 mg telmisartan. Plasma concentrations of telmisartan were determined by the high performance liquid chromatography-mass spectrometry method up to 48 h after telmisartan administration. Results: Interindividual variation for tmax, Cmax, t1/2, AUC0–48, AUC0–∞, and clearance (CL) for telmisartan was approximately 6-, 33-, 16-, 17-, 20-, and 20-fold, respectively. Cmax (p=0.010), t1/2 (p=0.029) and CL (p=0.010) of telmisartan were not normally distributed. MDR1 3435TT homozygotes seemed to show increases in Cmax, tmax, t1/2, AUC0–48, and AUC0–∞. However, no significant differences in Cmax, tmax, t1/2, AUC0–48, AUC0–∞, and CL among MDR1 C3435T genotypes were observed. Conclusions: MDR1 C3435T polymorphism does not affect oral pharmacokinetics of telmisartan. Clin Chem Lab Med 2009;47:38–43.