富马酸喹硫平缓释片在中国健康受试者中的生物等效性研究

目的研究富马酸喹硫平缓释片仿制药与原研药在中国健康受试者中单剂量空腹和餐后条件下给药的生物等效性。方法用单中心、开放、随机、单次给药、两制剂、两周期交叉设计,共纳入68例(空腹试验36例,餐后试验32例)成年男性和女性受试者随机交叉给药。分别单次口服受试制剂和参比制剂200 mg,用液相色谱-串联质谱(LC-MS/MS)法测定血浆中喹硫平的浓度。用SAS V9.4软件计算主要药代动力学参数。结果空腹组的富马酸喹硫平缓释片受试制剂和参比制剂主要药代动力学参数如下:AUC_0-t分别为(2432.45±859.54)和(2368.00±792.38)ng·mL^-1·h,AUC_0-∞分别为(2516.56±864.19)和(2461.20±803.72)ng·mL^-1·h,C_max分别为(206.88±92.00)和(207.16±109.88)ng·mL^-1,t_max分别为5.25和4.50 h,t1/2分别为(6.97±2.43)和(7.26±2.13)h。餐后组的富马酸喹硫平缓释片受试制剂和参比制剂主要药代动力学参数如下:AUC_0-t分别为(2774.99±1077.62)和(2856.20±1180.25)ng·mL^-1·h,AUC_0-∞分别为(2840.63±1076.46)和(2916.44±1174.10)ng·mL^-1·h,C_max分别为(398.78±142.90)和(373.15±142.99)ng·mL^-1,t_max分别为5.50和5.00 h,t1/2分别为(4.41±0.63)和(4.68±0.96)h。在空腹及餐后条件下,受试制剂与参比制剂主要药代动力学参数的90%置信区间均在80.00%~125.00%。结论在空腹及餐后条件下,中国健康成年受试者单次口服富马酸喹硫平缓释片仿制药与原研药具有生物等效性。

Bioequivalence study of quetiapine fumarate extend-release tablets in Chinese healthy adults

Objective To compare the pharmacokinetic properties and bioequivalence of the domestic and imported quetiapine fumarate extend-release tablets in Chinese healthy adults under fasting and fed conditions.Methods This randomized,single-center,open-label,single-dose,two-period crossover study assigned 68 healthy adults to receive a single 200 mg dose of quetiapine fumarate extend-release tablet(either domestic or imported tablet at one single period)under fasting(n=36 cases)or fed(n=32 cases)conditions.The drug was orally administrated.The plasma concentrations of the drug were quantified by LC-MS/MS method.The pharmacokinetic parameters including AUC_0-t,AUC_0-∞,t_maxand C_maxwere employed to test bioequivalence by SAS V9.4 software.Results Under fasting condition,the main pharmacokinetic parameters of quetiapine fumarate extend-release tablets were as follows:AUC_0-twere(2432.45±859.54)and(2368.00±792.38)ng·mL^-1·h,AUC_0-∞were(2516.56±864.19)and(2461.20±803.72)ng·mL^-1·h,C_maxwere(206.88±92.00)and(207.16±109.88)ng·mL^-1,t_maxwere 5.25 and 4.50 h,t1/2 were(6.97±2.43)and(7.26±2.13)h.Under fed condition,the main pharmacokinetic parameters of quetiapine fumarate extend-release tablets were as follows:AUC_0-twere(2774.99±1077.62)and(2856.20±1180.25)ng·mL^-1·h,AUC_0-∞were(2840.63±1076.46)and(2916.44±1174.10)ng·mL^-1·h,C_maxwere(398.78±142.90)and(373.15±142.99)ng·mL^-1,t_maxwere 5.50 and 5.00 h,t1/2 were(4.41±0.63)and(4.68±0.96)h.Under both conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test tablets and the reference tablets were between 80.00%and 125.00%,which met the criteria for bioequivalence evaluation.Conclusion Under both fasting and fed conditions,the domestic and imported quetiapine fumarate extend-release tablets were bioequivalent in Chinese healthy adults.