国产与进口替米沙坦制剂在人体内的药动学及生物等效性

目的:建立人血浆中替米沙坦浓度的高效液相色谱-质谱(HPLC-MS)分析方法,评价国产和进口替米沙坦制剂的生物等效性。方法:采用随机交叉试验方法,用HPLC-MS法对国产替米沙坦胶囊和进口替米沙坦片在20名中国健康男性受试者中的血药浓度进行测定。药动学参数用3P97程序进行计算。结果:国产与进口替米沙坦制剂的AUC_(0～t)分别是:(1 861±s 198)和(1 833±186)μg·h·L~(-1);c_(max)为(181±36)和(180±32)μg·L~(-1);t_(1/2)为(18.8±2.9)和(19±3)h。国产替米沙坦胶囊的相对生物利用度为(104±19)%。AUC_(0～t)、c_(max)经对数转换后方差分析和t检验表明两制剂生物等效。结论:HPLC-MS法测定替米沙坦简便,准确,灵敏度高。国产替米沙坦胶囊和进口替米沙坦片具有生物等效性。

Pharmacokinetics and bioequivalence of domestic and imported telmisartan in healthy male volunteers

AIM:To establish a HPLC-MS method for the study of pharmacokinetics and bioequivalence of telmisartan in human.METHODS:A randomized crossover design was performed in 20 healthy male volunteers.In the two study periods,a single 40 mg dose of each capsule or tablet was administered to each volunteer.The plasma concentration was determined by HPLC-MS method,and the pharmacokinetic parameters were calculated by the pharmacokinetic program 3P97.RESULTS:AUC_(0-t) of telmisartan for the test and reference preparations were (1 861±s 198) and (1 833±186)μg·h·L~(-1),c_(max) were (181±36) and (180±32)μg·L~(-1),t_(1/2) were (18.8±2.9) and (19±3) h,respectively.The relative bioavailability of the test preparation was (104±19)%.Bioequivalence results on logarithmic transformations of AUC_(0-t) and c_(max) were calculated by analysis of variance,t test and the results showed that the two preparations were bioequivalent. CONCLUSION:HPLC-MS method is sensitive,accurate and convenient for the determination of telmisartan. The domestic and imported telmisartan are bioequivalent.