琥珀酸普芦卡必利片在中国健康女性受试者中的生物等效性研究  

Bioequivalence of prucalopride succinate tablets in Chinese healthy women volunteers

作　　者：储继红[1] 殷俊刚 吴婷[1] 万瑶瑶 俞景梅[1] 居文政[1] 邹建东[1] 李长印[1] CHU Ji-hong;YIN Jun-gang;WU Ting;WAN Yao-yao;YU Jing-mei;JU Wen-zheng;ZOU Jian-dong;LI Chang-yin(Department of Clinical Pharmacology,Affiliated Hospital to Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院临床药理科,南京210029

出　　处：《中国新药杂志》2022年第8期767-772,共6页Chinese Journal of New Drugs

摘　　要：目的:评价国产琥珀酸普芦卡必利片和进口琥珀酸普芦卡必利片在中国健康女性受试者空腹和餐后状态下的生物等效性.方法:采用随机、开放、双周期交叉设计,空腹组和餐后组受试者各24例,每周期口服受试制剂(T)或参比制剂(R)2 mg.采用经过验证的LC-MS/MS方法测定血浆普芦卡必利的浓度,用WinNonlin 7.0软件计算药动学参数,用SAS 9.4软件评价生物等效性.结果:空腹组受试制剂与参比制剂的药动学参数分别为:血药峰浓度(C_(max))为(4.37±0.94)和(4.28±0.73)ng·mL^(-1),0~72 h血药浓度-时间曲线下面积(AUC_(0-72h))为(73.86±13.34)和(77.52±12.26)h·ng·mL^(-1),血药浓度-时间曲线下总面积(AUC_(0-∞))为(78.62±14.77)和(82.70±14.10)h·ng·mL^(-1),达峰时间(T_(max))为1.5(1,4)和1.5(1,4)h,药物半衰期(t_(1/2))为(18.13±1.99)和(18.08±2.32)h.餐后组受试制剂与参比制剂的药动学参数分别为:C_(max)为(4.07±1.05)和(4.25±0.55)ng·mL^(-1),AUC_(0-72h)为(71.83±13.32)和(77.67±9.64)h·ng·mL^(-1),AUC_(0-∞)为(76.82±14.58)和(83.19±10.72)h·ng·mL^(-1),T_(max)为2.0(1,5)和2.0(1,5)h,t_(1/2)为(18.54±2.18)和(18.50±2.04)h.在空腹和餐后状态下,C_(max),AUC_(0-72h),AUC_(0-∞)几何均值比(T/R)的90%置信区间均在80.00%~125.00%范围内.结论:国产琥珀酸普芦卡必利片和进口琥珀酸普芦卡必利片在中国健康女性受试者空腹和餐后状态下均具有生物等效性.Objective:To evaluate the bioequivalence of domestic prucalopride succinate tablets and imported prucalopride succinate tablets under fasting and fed conditions in Chinese healthy women volunteers.Methods:A randomized,open,double-phase crossover design was adopted.Twenty-four female volunteers participated in fasting or fed trial were randomly divided into two groups receiving a single dose(2 mg)of test tablets(T)or reference tablets(R),respectively.A validated LC-MS/MS method was used to detect the plasma concentrations of prucalopride.The pharmacokinetic parameters were calculated with WinNonlin 7.0 software.The bioequivalence was evaluated by SAS 9.4 software.Results:The pharmacokinetic parameters of the test formulations and reference formulations under fasting condition were as follows:C_(max)(4.37±0.94)and(4.28±0.73)ng·mL^(-1),AUC_(0-72h)(73.86±13.34)and(77.52±12.26)h·ng·mL^(-1),AUC_(0-∞)(78.62±14.77)and(82.70±14.10)h·ng·mL^(-1),T_(max)1.5(1,4)and 1.5(1,4)h,t_(1/2)(18.13±1.99)and(18.08±2.32)h,respectively.The pharmacokinetic parameters of the test formulations and reference formulations under fed condition were as follows:C_(max)(4.07±1.05)and(4.25±0.55)ng·mL^(-1),AUC_(0-72h)(71.83±13.32)and(77.67±9.64)h·ng·mL^(-1),AUC_(0-∞)(76.82±14.58)and(83.19±10.72)h·ng·mL^(-1),T_(max)2.0(1,5)and 2.0(1,5)h,t_(1/2)(18.54±2.18)and(18.50±2.04)h,respectively.The 90%confidence intervals for the geometric mean ratio(T/R)of C_(max),AUC_(0-72h),AUC_(0-∞)under fasting and fed conditions were within the bioequivalence acceptance range of 80.00%~125.00%.Conclusion:Domestic prucalopride succinate tablets and imported prucalopride succinate tablets are bioequivalent in Chinese healthy women volunteers under fasting and fed conditions.

关 键 词：普芦卡必利 生物等效性 中国健康女性 药动学 

分 类 号：R969.1[医药卫生—药理学]