在中国五个不同种族人群中洛沙坦及其活性羧酸代谢物 E-3174 的药代动力学研究。

Pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 in five ethnic populations of China.

机构信息

Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

J Clin Pharm Ther. 2012 Apr;37(2):226-31. doi: 10.1111/j.1365-2710.2011.01279.x. Epub 2011 Jul 21.

DOI:10.1111/j.1365-2710.2011.01279.x

PMID:21777404

Abstract

WHAT IS KNOWN AND OBJECTIVE

Interethnic variability in drug pharmacokinetics is well known. Our aim was to investigate whether the pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 vary between subjects of five Chinese ethnicities (Han, Mongolian, Korean, Hui and Uigur).

METHODS

Fifty healthy subjects (five men and five women of each ethnicity) were recruited, and each received 50-mg dose of losartan in tablet form. Fourteen blood samples were collected for each subject over a 24-h period after drug administration. The concentrations of losartan and its active carboxylic acid metabolite E-3174 in plasma were determined by high-performance liquid chromatography/fluorescence (HPLC/FLU) method, and the pharmacokinetic parameters were calculated by DAS 2.0 software and compared by SPSS 16.0 software. Pharmacokinetic parameters, including area under the curve from 0h to the last measured point 24h [AUC((0-24))], area under the curve from 0h to infinite time [AUC((0-∞))], peak plasma concentration (C(max) ), time to reach C(max) (t(max) ), oral clearance (CL), oral volume of distribution (V(d)) and elimination half-life (t(1/2) ), were determined following a single oral dose of losartan.

RESULTS AND DISCUSSION

The t(1/2) values of losartan and its active carboxylic acid metabolite E-3174 showed significant differences across the five ethnicities. After normalization by weight, no ethnicity-based difference was noted in the pharmacokinetic parameters of losartan. However, there were significant differences in C(max) and V(d) of the active carboxylic acid metabolite E-3174 for Han and Mongolian subjects, compared with the other three ethnic groups. There was a high linear correlation between weight and C(max) , AUC((0-24)) , AUC((0-∞)) , CL and V(d) .

WHAT IS NEW AND CONCLUSION

Ethnicity was associated with significant differences in the single-dose pharmacokinetics of losartan's active carboxylic acid metabolite E-3174 in healthy subjects of the five main ethnic groups in China.

摘要

已知和目的

药物药代动力学的种族间变异性是众所周知的。我们的目的是研究 5 种中国人种（汉族、蒙古族、朝鲜族、回族和维吾尔族）的洛沙坦及其活性羧酸代谢物 E-3174 的药代动力学是否存在差异。

方法

招募了 50 名健康受试者（每个种族 5 名男性和 5 名女性），并给他们服用 50mg 洛沙坦片。给药后 24 小时内，每个受试者采集 14 个血样。用高效液相色谱/荧光（HPLC/FLU）法测定血浆中洛沙坦及其活性羧酸代谢物 E-3174 的浓度，并用 DAS 2.0 软件计算药代动力学参数，并通过 SPSS 16.0 软件进行比较。药代动力学参数包括 0 到最后测量点 24 小时的曲线下面积[AUC((0-24))]、0 到无限时间的曲线下面积[AUC((0-∞))]、峰血浆浓度（C(max)）、达到 C(max)的时间（t(max)）、口服清除率（CL）、口服分布容积（V(d)）和消除半衰期（t(1/2)），是在单次口服洛沙坦后确定的。

结果与讨论

洛沙坦及其活性羧酸代谢物 E-3174 的 t(1/2)值在 5 个人种之间存在显著差异。经体重归一化后，洛沙坦的药代动力学参数在人种之间无差异。然而，汉族和蒙古族受试者的活性羧酸代谢物 E-3174 的 C(max)和 V(d)与其他三个种族存在显著差异。体重与 C(max)、AUC((0-24))、AUC((0-∞))、CL 和 V(d)之间存在高度线性相关。