盐酸舍曲林片、分散片人体生物等效性研究

Bioequivalence of oral sertraline hydrochloride tablets and dispersible tabletsin healthy volunteers

目的评价盐酸舍曲林片、分散片在健康人体相对生物利用度及生物等效性。方法受试者随机、自身三交叉、单剂量口服受试制剂盐酸舍曲林片、分散片和参比制剂50 mg,采用LC/MS/MS法测定血浆中药物浓度,药动学参数采用BAPP2.2软件处理获得。结果3种制剂Cmax分别为(14.10±6.49)ng/ml、(14.17±6.02)ng/ml和(14.51±6.27)ng/ml,Tmax分别为(5.22±1.17)h、(5.11±1.68)h和(4.72±1.18)h,t1/2分别为(29.92±7.43)h、(27.55±6.89)h和(29.04±7.52)h,AUC0tn分别为(457.86±236.28)ng/(ml.h)、(452.62±259.41)ng/(ml.h)和(452.49±275.10)ng/(ml.h),AUC0-∞分别为(502.95±276.04)ng/(ml.h)、(493.11±299.28)ng/(ml.h)和(502.59±324.23)ng/(ml.h);相对于参比制剂,受试制剂的生物利用度F0-tn为(105.22±21.85)%和(13.26±19.00)%。受试制剂和参比制剂的Cmax、AUC0-tn和AUC0-∞经对数转换后进行方差分析,两制剂间无显著性差异。结论浙江京新药业股份有限公司研制的盐酸舍曲林片、盐酸舍曲林分散片与辉瑞制药有限公司生产的盐酸舍曲林片具有生物等效性。

Objective To study the bioavailability and bioequivalence of the tested and reference sertraline hydrochloride （tablets and dispersible tablets） in healthy male volunteers.Methods According to the 3 - way crossover design,each volunteer was given orally 50 mg sertraline hydrochlofide. The plasma concentrations were determined by LC/MS/MS. Pharmacokinetic parameters were obtained using BAPP 2.2 program. Results Cmar were（14.10±6.49）μg/ml, （14.17 ± 6.02） μg/ml and（14.51μ6.27） μg/ml,Tmax were （5.22± 1.17） h, （5.11± 1.68） h and（4.72±1.18） h, T1/2 were（29.92 ± 7.43） h, （27.55± 6.89） h and （29.04 ± 7.52） h, AUC0-∞ were （457.86±236.28） ±g/（ml·h）,（452.62 ± 259.41） μg/（ml·h） and （452.49±275.10） μg/（ml·h）,AUC0-∞ were （502.95± 276.04） μg/（ml·h）,（493.11 ± 299.28） btg,/（ml·h） and （502.59±324.23） μg/（ml·h）, respectively. The relative bioavailability was （ 105.22 ± 21.85） % and（ 103.26 ±19.00） %. The data of the reference and tested drugs were up to the standard of bioequivalence as shown by F test. Conclusions Two samples of sertraline hydrochloride tablets and one sample of dispersible tablet made in two different pharmaceutical companies are bioequivalent.