国产盐酸舍曲林胶囊和片剂的人体药物动力学及生物等效性

Pharmacokinetics and bioequivalence of domestic sertraline hydrochloride capsules and tablets in healthy volunteers

目的研究国产盐酸舍曲林胶囊及片剂的相对生物利用度、药物动力学特征及生物等效性.方法采用随机、开放、3×3拉丁方设计实验,18名男性健康受试者分别单剂量口服含舍曲林50 mg的试验片剂、胶囊及参比制剂.采用HPLC-MS/MS/MS法测定给药后不同时间的血药浓度,计算3者的药物动力学参数及评价其生物等效性.结果 18例健康志愿者口服参比制剂和试验制剂舍曲林胶囊及片剂后,参比制剂中舍曲林的主要药物动力学参数cmax为(10.14±3.43)μg·L-1;tmax为(4.44±1.10)h;AUC0～96为(262.82±100.66)μg·h·L-1;t1/2为(29.19±4.91)h.试验制剂片剂中舍曲林的主要药物动力学参数cmax为(10.16±3.22)μg·L-1;tmax为(4.33±1.85)h;AUC0～96为(269.71±107.47)μg·h·L-1;t1/2为(30.99±6.49)h.试验制剂胶囊中舍曲林的主要药物动力学参数cmax为(10.39±3.59)μg·L-1;tmax为(4.94±1.30)h;AUC0～96为(264.45±112.57)μg·h·L-1;t1/2为(29.68±5.25)h.试验制剂片剂和胶囊分别对参比制剂的相对生物利用度F为(103.4%±18.2%)、(99.8%±13.6%).结论经统计学分析,国产试验制剂胶囊剂和片剂与参比制剂具有生物等效性.

OBJECTIVE To study the pharmacokinetics,relative bioequivalence of domestic sertraline hydrochloride capsules and tablets in 18 healthy volunteers. METHODS A single oral dose of 50 mg domestic sertraline hydrochloride capsules,tablets and their contrastive tablets was given to healthy volunteers in an open randomized 2 way crossover design. The plasma concentrations were determined by HPLC/MS/MS method. RESULTS The main pharmacokinetic parameters of sertraline were as follows:c_ maxwas(10.14±3.43)μg·L -1,(10.16±3.22)μg·L -1 and(10.39±3.59)μg·L -1;t_ maxwas(4.44±1.10)h,(4.33±1.85)and(4.94±1.30)h;t_ 1/2was(29.19±4.91)h,(30.99±6.49)h and(29.68±5.25)h;AUC_ 0～96was(262.82±100.66)μg·h·L -1,(269.71±107.47)μg·h·L -1and(264.45±112.57)μg·h·L -1for the reference tablets,sertraline tablets and capsules,respectively. The relative bioavailability of domestic sertraline hydrochloride capsules and tablets were(99.8%±13.6%)and(103.4%±18.2%)respectively. CONCLUTIONS Statistic analysis showed that the reference preparation and the test preparation were bioequivalent.