OATP1B1基因多态性对匹伐他汀钙片在中国汉族健康受试者体内的药代动力学影响

Effects of organic anion transporting polypeptide 1B1 polymorphism on the pharmacokinetics of pitavastatin calcium tablet in healthy subjects of Chinese Han population

目的:研究有机阴离子转运多肽OATP1B1基因多态性对匹伐他汀钙片在中国汉族健康受试者体内的药代动力学影响。方法:用PCR-RFLP对筛选出的36名合格受试者进行OATPlBl A388G、OATPlBl T521C基因分型,受试者单剂量口服匹伐他汀钙片2 mg,用HPLC-MS-MS法测定血浆匹伐他汀钙片浓度。结果:匹伐他汀钙片药代动力学参数显示,与388AA型相比,388AG型AUC0-10增加26%,t1/2增加30%;与521TT型相比,521TC型AUC0-10增加23.6%,CL/F降低20.8%。可能由于突变例数太少,导致OATP1B1 A388G和OATP1B1 T521C突变组和野生组各药代动力学参数(t1/2、tmax、Cmax、AUC0-t、AUC0-inf、CL/F、Vd/F)之间差异无明显统计学意义。结论:OATP1B1基因多态性可能对中国汉族人群中匹伐他汀钙片代谢无影响。

Objective： To investigate the influence of organic anion transporting polypeptide 1B1 polymorphism on the pharmacokinetics of pitavastatin calcium tablets in healthy subjects of Chinese Han population.Methods： Apply PCR-RFLP to measure the genetypes of OATP1B1 A388G,OATPlBl T521C in 36 healthy subjects.Each was given a single oral dose of 2 mg pitavastatin calcium tablet.The plasma concentrations of pitavastatin calcium tablet were measured by HPLC-MS-MS.Results： The AUC0-10 of pitavastatin calcium tablet significantly increased 26%,and t1/2 increased 30% in subjects expressing the 388AG genotype compared with 388AA subjects.The AUC0-10 of pitavastatin calcium tablets increased 23.6%,and CL/F decreased 20.8% in subjects expressing the 521TC genotype compared with 521TT subjects.The parameters（t1/2,tmax,Cmax,AUC0-t,AUC0-inf,CL/F,Vd / F） had no significant statistical difference in mutate group and wild group of OATP1B1 A388G and OATP1B1 T521C.Conclusion： The OATP1B1 polymorphism may have no effect on the pharmacokinetics of pitavastatin calcium tablet in Chinese Han population.