国产氟哌噻吨美利曲辛人体生物等效性研究

目的：研究单剂量口服国产和进口氟哌噻吨美利曲辛片在健康受试者体内的药动学特征,评价其是否具有生物等效性。方法：采用随机、双交叉试验设计。22名健康男性受试者分别单次口服氟哌噻吨美利曲辛片10 mg（2片）后血浆中氟哌塞吨和美利曲辛的浓度采结果：国产和进口制剂中氟哌噻吨峰浓度Cmax分别为164.8±55.2和161.5±51.9 pg.mL-1;达峰时间Tmax用LC-MS/MS法检测,药动学参数用SigmaPLot 2001和Orign 6.0软件程序计算。分别为9.0±4.5和9.6±3.9 h,AUC0→t分别为5 622±2 243和5412±1 677 pg.h-1;美利曲辛Cmax分别为10.9±6.2和9.6±4.4 ng.mL-1;Tmax分别为4.7±0.9和4.4±1.1 h。AUC0→t分别为312±155和291±139 ng.h-1;国产及进口制剂的Cmax、AUC0→120 h、AUC0→∞等药动学参数经对数转换后的统计学处理（方差分析及双单侧t检验）,国产与进口制剂药物间差异均无统计学意义（P〉0.05）。国产制剂的相对生物利用度氟哌噻吨为103.2±19.9%,美利曲辛为107.1±14.5%（n=22）。结论：国产与进口氟哌噻吨美利曲辛片具有生物等效性。

Human Bioequivalence Study of Domestic and Imported Flupentixo! and Melitracen Tablets

Objective: To study the pharmacokinetics and bioequivalence of domestic and imported Flupentixol and Melitracen tablets in healthy subjects.Methods: Twenty-two healthy male subjects in a randomized crossover design were given a single oral dose of 10 mg domestic and imported Flupentixol and Melitracen tablets.Plasma concentrations of the subjects were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters were calculated applied SigmaPLot 2001 and Origin 6.0 software.Results: The main pharmacokinetic parameters of domestic and imported Flupentixol and Melitracen were as follows.Flupentixol: Cmax were 164.8 ± 55.2 and 161.5 ± 51.9 pg·mL-1;Tmax were 9.0 ± 4.5 and 9.6 ± 3.9 h;AUC0→t were 5 622 ± 2 243 and 5 412 ± 1 677 pg·h-1,respectively.Melitracen: Cmax were 10.9 ± 6.2 and 9.6 ± 4.4 ng·mL-1;Tmax were 4.7 ± 0.9 and 4.4 ± 1.1 h;AUC0→t were 312 ± 155 and 291 ± 139 ng·h-1,respectively.The statistic analysis of two formulations was conducted by analysis of variance,two one-sided tests and confidence intervals,which demonstrated that there were no significant differences between domestic and imported formulations in main pharmacokinetic parameters(P > 0.05).The mean relative bioavailability of domestic formulation of Flupentixol was 105.42 ± 22.23%,and Melitracen was 107.29 ± 20.40%(n=24).Conclusion: The domestic Flupentixol and Melitracen are bioequivalent to the imported formulation.