酒石酸美托洛尔片在健康人体中的生物等效性研究

Bioequivalence of metoprolol tartrate tablets in healthy volunteers

目的:研究国产与进口酒石酸美托洛尔片的生物等效性。方法:采用双交叉随机自身对照试验设计,20名健康男性志愿者分别单剂口服2种酒石酸美托洛尔片(参比制剂和受试制剂)100 mg,应用高效液相-荧光检测法测定血浆中美托洛尔的浓度,经DAS 2.1软件处理后得药动学数据,并进行等效性检验。结果:参比制剂与受试制剂的主要药动学参数分别为C_(max)(457.2±112.6)和(480.9±107.6)ng·mL^(-1),T_(max)(1.43±0.34)和(1.25±0.44)h,t_(1/2)(3.20±0.97)和(3.48±1.36)h,AUC_(0-24h)(2 241±864)和(2 169±873)ng·h·mL^(-1),AUC_(0-∞)(2199±889)和(2264±870)ng·h·mL^(-1),受试制剂对参比制剂的平均相对生物利用度为(104.6±16.9)%。将主要药动学参数经方差分析和双单侧t检验,T_(max)采用非参数检验,结果显示,差异无统计学意义。结论:2种酒石酸美托洛尔片具有生物等效性。

Objective：To study the bioequivalence between domestic and exotic metoprolol tartrate tablets in healthy volunteers. Methods： In a randomized, crossover and self-control study, 20 healthy male volunteers were orally administrated with a single crossover dose of either metoprolol tartrate tablets （ 100 mg）. The plasma samples were collected to measure metoprolol concentrations by HPLC-fluorometry. The plasma concentration-time curves as well as bioequivalence of both metoprolol tartrate tablets were analyzed using DAS 2.1 software. Results： The main pharmacokinetic parameters of the exotic and domestic tablets were as follow： Cmax（457.2±112.6） and （480.9 ±107.6 ） ng·mL^-1 ; Tmax（1.43 ± 0.34） and （1.25 ±0.44） h; t1/2（3.20±0.97） and （3.48±1.36） h; AUC0-24h（2241 ±864） and （2 169 ±873） ng·h·mL^-1 ; AUC0-∞ （2 199 ±889） and （2 264 ±870） ng·h·mL^-1. The relative bioavailability of domestic tablets was （104.6± 16.9） %. There were no statistically significant differences between 2 tablets as analyzed with ANOVA and two-one-sided t-test. Conclusion： The domestic and exotic metoprolol tartrate tablets are bioequivalent.