替米沙坦片的药物动力学和生物等效性研究

目的：研究替米沙坦片在正常人体内的药物动力学行为。方法：采用随机交叉设计，18例健康男性受试者随机交叉口服国产替米沙坦片和进口片剂，服药后0．5～72h内间隔取血。血样加入内标扎来普隆经预处理后用HPLC—FLD测定。采用3P97药物动力学程序拟合主要药动学参数，并以进口片剂为参比制剂，估算国产替米沙坦片的生物利用度，判断生物等效性。结果：替米沙坦参比片和供试片的药-时曲线均符合二房室模型，其AUC0-72分别为（2307．4±1697．8）ng·h·ml^-1和（2359．1±1204．7）ng·h·ml^-1；AUC0-∞分别为（2408．4±1809．0）ng·h·ml^-1和（2485．9±1318．7）ng·h·ml^-1，Cmax分别为（520．07±159．47）ng·ml^-1和（520．59±136．52）ng·ml^-1，tmax分别为（0．94±0．29）h和（0．94±0．24）h。以进口片为对照，用AUC0-72计算的国产片生物利用度为（112．20±25．87）％；用AUC0-∞计算的国产片生物利用度为（112．47±24．29）％。结论：本实验建立的分析方法灵敏、准确、简便，统计学结果表明两制剂生物等效。

Bioequivalence and Pharmacokinetics of Telmisartan Tablets in Chinese Healthy Volunteers

Objective： To develop an HPLC assay for determination of telmisartan in human plasma and to investigate the pharmacokinetics and bioequivalence of telmisartan tablet in healthy volunteers. Method： An open randomized crossover design was performed in 18 healthy volunteers. In the two study periods, a single 80 mg dose of either tested or reference telmisartan tablets was administered to each volunteer, telmisartan was determined by high performance liquid chromatography fluorescence detector method. The pharmacokinetic parameters and relative bioavailability were calculated on the basis of compartment models by using 3P97 program to evaluate the hioequivalence of 2 preparations. Result： The concentration-time curves of 2 products were fitted to two compartment models with oral absorption. The main pharmaeokinetie parameters were followed： AUC0-72, Cmax, T1/2β/h and Tmax of the reference drug and tested drug were （2307.4±1697.8） ng·L^-1 .h , （520.07±159.47）ng·L^-1（18.69±5.83）h,（ 0.94 ±0.29）h and （2359.1±1204. 7） ng·h·L^-1 , （ 520.59 ± 136.52） ng·L^-1 , （ 16.89 ± 4.60） h , （0.94 ± 0.24） h respectively. The relative bioavailability of the telmisartan tested tablet was （ 112.20 ± 25.87 ） %. These main pharmacokinetic parameters obtained showed no statistically significant difference between 2 products （P 〉 0.05 ）. Conclusion： The assay was shown to be sensitive, accurate and convenient. Both preparations are bioequivalent.