盐酸依匹斯汀片在健康人体内的生物等效性试验  

Bioequivalence study of epinastine hydrochloride tablets after single dose administration in healthy volunteers

作　　者：杨克旭[1] 荆珊[1] 高鹍 李星宇 谭莉[1] 刘文芳[1] 鲁春艳[1] 林阳[1] YANG Ke-xu;JING Shan;GAO Kun;LI Xing-yu;TAN Li;LIU Wen-fang;LU Chun-yan;LIN Yang(Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;GreenPine Pharma Group Co.,Ltd.,Tianjin 300308,China)

机构地区：[1]首都医科大学附属北京安贞医院,北京100029 [2]青松医药集团股份有限公司,天津300308

出　　处：《中国新药杂志》2022年第12期1178-1182,共5页Chinese Journal of New Drugs

摘　　要：目的:评价健康成年受试者交叉给予受试制剂盐酸依匹斯汀片和参比制剂依匹斯汀片(商品名:爱理胜)在空腹和餐后状态时的生物等效性以及受试制剂盐酸依匹斯汀片的安全性。方法:本研究采用随机、开放、单剂量、双周期、交叉对照试验设计,空腹试验和餐后试验各入组健康男性和女性24例,单剂量空腹及餐后口服受试制剂和参比制剂。采用液相色谱-串联质谱法(LC-MS/MS)测定血浆依匹斯汀浓度。使用Phoenix WinNonlin软件6.3版,采用非房室模型计算药动学参数,采用平均生物等效性评价方法进行等效性评价。结果:空腹试验受试制剂和参比试剂的峰浓度(C_(max))分别为(25.03±6.08)和(25.66±8.16)ng·mL^(-1),达峰时间(T_(max))分别为2.0(1.0,4.0)和2.0(1.0,4.0)h,t_(1/2)分别为(8.6±1.5)和(8.4±1.2)h,0-t时间的血药浓度-时间曲线下面积(AUC_(0-t))分别为(249.40±50.30)和(268.11±86.05)h·ng·mL^(-1),AUC_(0-∞)分别为(254.85±50.79)和(273.61±87.58)h·ng·mL^(-1);餐后试验受试制剂和参比试剂的C_(max)分别为(15.64±5.25)和(14.41±3.51)ng·mL^(-1),T_(max)分别为2.8(1.0,6.0)和3.0(1.0,4.0)h,t_(1/2)分别为(9.9±2.0)和(9.4±1.5)h,AUC_(0-t)分别为(143.49±28.00)和(139.15±25.68)h·ng·mL^(-1),AUC_(0-∞)分别为(148.20±28.69)和(143.61±26.62)h·ng·mL^(-1)。空腹组和餐后组,受试制剂和参比制剂的AUC_(0-t),AUC_(0-∞)和C_(max)的几何均值比值(受试制剂/参比制剂)的90%置信区间(90%CI)均介于80%~125%的等效范围内。结论:受试制剂与参比制剂在空腹及餐后服用的情况下具有生物等效性。Objective:To evaluate the bioequivalence of reference and test formulations of epinastine hydrochloride tablets after single dose administration in healthy Chinese volunteers under fasting and fed conditions and evaluate the safty of the test formulations.Methods:24 male and 24 female healthy volunteers participated in a randomized,open,single-dose,double-cycle,crossover study under fasting and fed conditions.Plasma concentration of epinastine after administration was analyzed by LC-MS/MS method.Non-compartmental pharmacokinetic parameters were calculated by phoenix WinNonlin 6.3,and bioequivalence was evaluated using average bioequivalence method.Results:For the test and reference formulations under fasting condition,the C_(max)of epinastine were(25.03±6.08)and(25.66±8.16)ng·mL^(-1),T_(max) were 2.0(1.0,4.0)and 2.0(1.0,4.0)h,t_(1/2)were(8.6±1.5)and(8.4±1.2)h,AUC_(0-t) were(249.40±50.30)and(268.11±86.05)h·ng·mL^(-1),AUC_(0-∞)were(254.85±50.79)and(273.61±87.58)h·ng·mL^(-1),respectively.For the test and reference formulations under fed condition,the C_(max)of epinastine were(15.64±5.25)and(14.41±3.51)ng·mL^(-1),T_(max) were 2.8(1.0,6.0)and 3.0(1.0,4.0)h,t_(1/2)were(9.9±2.0)and(9.4±1.5)h,AUC_(0-t) were(143.49±28.00)and(139.15±25.68)h·ng·mL^(-1),AUC_(0-∞)were(148.20±28.69)and(143.61±26.62)h·ng·mL^(-1),respectively.The geometric mean ratios(GMR)of AUC_(0-t),AUC_(0-∞)and C_(max)between test and reference formulations were within the 90%confidence interval of regular bioequivalent range(80%to 125%).Conclusion:The two formulations are bioequivalent under fasting and fed conditions.

关 键 词：盐酸依匹斯汀片 健康受试者 生物等效性 敏感性分析 

分 类 号：R969.4[医药卫生—药理学]