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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 relative bioavailability, pharmacokinetics and bioequivalence of domestic sertraline capsules and tablets. Methods A randomized, open, 3 × 3 Latin square design experiment was conducted. Eighteen male healthy subjects were orally given test tablets, capsules and reference preparations containing sertraline 50 mg respectively. The plasma concentrations at different time points after drug administration were determined by HPLC-MS / MS / MS. The pharmacokinetic parameters and the bioequivalence of the three drugs were calculated. Results The main pharmacokinetic parameters cmax of sertraline in reference preparations were (10 14 ± 3 43) μg · L -1 after oral administration of reference formulation and test preparation of sertraline capsules and tablets in 18 healthy volunteers ; tmax was (4.44 ± 1.10) h; AUC0-96 was (262. 82 ± 100.66) μg · h · L-1; t1 / 2 was (29 19 ± 4 91) h. The main pharmacokinetic parameters cmax of sertraline in the test preparations were (10 16 ± 3 22) μg · L-1; tmax was (4.33 ± 1.85) h; AUC0-96 was (269.71 ± 107. 47) μg · h · L-1; t1 / 2 was (30.99 ± 6.94) h. The main pharmacokinetic parameters cmax of sertraline in the test preparation capsule were (10. 39 ± 3.59) μg · L-1; tmax was (4.94 ± 1.30) h; AUC0-96 was (264.45 ± 112. 57) μg · h · L-1; t1 / 2 was (29.68 ± 5.25) h. The relative bioavailability F of the test formulation tablets and capsules to the reference formulation was (103.4% ± 18.2%), (99.8% ± 13.6%), respectively. Conclusion According to the statistical analysis, the domestic test preparation capsules and tablets are bioequivalent to the reference preparations.