螺内酯片健康人体药动学及生物等效性评价

目的:研究螺内酯在中国健康人体内的药动学和生物等效性。方法:采用随机双周期交叉设计, 18名健康志愿者单剂量口服200 mg螺内酯,HPLC法测定血浆中螺内酯的代谢物坎利酮的浓度。结果:参比制剂和受试制剂药-时曲线均符合一房室模型,受试制剂和参比制剂的代谢物坎利酮的药动学参数如下:t_(mux)分别为(4．2±s 1．2)和(4．7±1．6)h,C_(mux)分别为(160±47)和(150±43)μg·L~(-1),t_(1/2ke)分别为(18±5)和(19±4)h,AUC_(0～72)分别为(3168±688)和(3267±627)μg·h·L~(-1),AUC_(0～∞)分别为(3611±768)和(3759±642)μg·h·L~(1-)。与参比制剂相比,受试制剂的相对生物利用度为(106±26)％。结论:所建立的方法适用于螺内酯的人体药动学研究;经方差分析和双向单侧t检验证明,2种制剂具有生物等效性。

Pharmacokinetics and bioequivalence of spironolactone tablets in healthy volunteers

AIM:To study the pharmacokinetics and bioequivalence of spironolactone in Chinese healthy people.METHODS:Two periods crossover randomized study was carried out in two groups with eighteen healthy male volunteers receiving a single dose of spironolactone 200 mg including two preparations, respectively.A sensitive and specific HPLC method was developed to quantitate the levels of canrenone in plasma,which was the metabolite of spironolactone.RESULTS:The concentration-time curves of canrenone coincided with a one-compartment open model.The main pharmacokinetic parameters of the trial and reference preparation weret t_(max)(4.2±s 1.2)and(4.7±1.6)h,c_(max)(160±47)and(150±43)μg·L-~(-1),t_(1/2ke)(18±5)and(19±4)h,AUC_(0-72)(3168±688)and(3267±627)μg·h·L~(-1),AUC_(0_∞)(3611±768)and(3759±642),respectively.The relative bioavailability of the trial preparation was(106±26)%.CONCLUSION: The HPLC method is suitable for the pharmacokinetie study of spironolaetone.Two one-sided t test and analysis of variance were performed in bioequivalent assessment,proving the two preparations of spironolactone are bioequivalent.