盐酸曲美他嗪片人体药动学和生物等效性评价

Pharmacokinetics and bioequivalence of trimetazidine dihydrochloride tablet in healthy volunteers

目的:评价国产与进口盐酸曲美他嗪片在健康人体的生物等效性。方法:20名健康男性受试者按两制剂两周期的交叉试验设计口服单剂量20mg的参比制剂和受试制剂后,采用高效液相色谱-质谱联用测定血浆中曲美他嗪的浓度,使用DAS1.0软件计算各药动学参数并进行生物等效性统计分析。结果:参比制剂和受试制剂的Cmax分别为(65.1±11.8)和(65.0±13.6)μg.L-1;tmax分别为(1.9±0.5)和(2.2±0.8)h;AUC0-24h分别为(576.6±112.8)和(591.5±119.6)μg.L-1.h;t1/2分别为(5.4±0.5)和(5.5±0.6)h。受试制剂的相对生物利用度为(102.8±8.8)%(AUC0-24h,T/AUC0-24h,R×100%)。结论:国产与进口盐酸曲美他嗪片具有生物等效性。

OBJECHVE To study the relative bioavailability of domestic and imported trimetazidine dihydrochloride tablets in healthy human subjects and its bioequivalence. METHODS In a randomized crossover study, 20 healthy male volunteers was given a single oral dose of 20 mg trimetazidine dihydrochloride tablets. The concentration of trimetazidine in plasma was determined by HPLC- MS. The pharmacokinetic parameters were processed by DAS program for statistic analysis. RESULTS The pharmacokinetic parameters of the test and reference tablets were as follows： Cmax were（65. 0 ± 13. 6） and （65. 1 ± 11.8）μg·L^-1; tmax were （2. 2 ± 0. 8） and （1.9 ± 0. 5） h; AUC（0-24h） were（591.5 ± 119. 6） and （576. 6 ± 112. 8）μg·L^-1 ·h; t（1/2） were（5. 5 ± 0. 6） and （5. 4 ± 0. 5）h, respectively. The relative bioavailability of the test tablets was （102. 8 ± 8. 8） %. There was no significant difference in tmax, Cmax, AUC（0-24h） and between the two preparations. The 90% confidential interval of Cmax and AUC（0-24h） were between 95. 0% - 103. 5% and 99. 1% - 106. 0% of those of reference tablets. CONCLUSION The domestic and imported trimetazidine dihydrochloride tablet were bioequivalent.