琥珀酸索利那新片在中国健康受试者的生物等效性研究

目的:评价中国健康受试者空腹及餐后单次口服琥珀酸索利那新受试制剂和参比制剂的生物等效性。方法:采用单中心、随机、开放、两周期交叉设计,空腹组和餐后组受试者各24例,每周期口服受试制剂或参比制剂10 mg,采用LC-MS/MS法测定索利那新血药浓度,WinNonlin 7.0软件计算药动学参数,并进行生物等效性评价。结果:空腹组受试制剂与参比制剂的药动学参数分别为:C max(13.99±3.34)和(13.27±3.20)ng/mL,AUC 0-t(675.60±210.46)和(653.31±238.59)h·ng·mL^-1,AUC 0-∞(728.28±240.20)和(718.14±275.63)h·ng·mL^-1,t max(5.00±1.41)h和(4.98±1.07)h,t 1/2(39.19±9.29)和(42.44±12.66)h,相对生物利用度按AUC 0-t计算为105.06%,按AUC 0-∞计算为104.07%。餐后组受试制剂与参比制剂的药动学参数分别为:C max(15.65±5.30)和(15.02±4.42)ng/mL,AUC 0-t(808.85±271.19)和(793.76±256.78)h·ng·mL^-1,AUC 0-∞(917.02±347.82)和(875.49±310.77)h·ng·mL^-1,t max(4.29±1.48)h和(5.69±4.10)h,t 1/2(49.47±20.08)和(45.29±12.24)h,相对生物利用度按AUC 0-t计算为100.91%,按AUC 0-∞计算为102.97%。空腹/餐后条件下两制剂的主要药动学参数C max、AUC 0-t、AUC 0-∞几何均数比值的90%置信区间均在80.00%~125%。结论:琥珀酸索利那新的受试制剂和参比制剂在空腹和餐后条件下,均生物等效。

Bioequivalence of solifenacin succinate tablets in healthy Chinese volunteers

AIM:To evaluate the bioequivalence of the test and reference preparations of solifenacin succinate tablets administered once orally under fasting and fed conditions in Chinese healthy volunteers.METHODS:The study was designed as single-center,randomized,open,self-crossover and twenty four healthy volunteers were recruited respectively in fasting and fed conditions.Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 10 mg.The plasma concentration of solifenacin was analyzed by LC-MS/MS.The major pharmacokinetic parameters were calculated by WinNonlin 7.0,then the bioequivalence was evaluated.RESULTS:The main pharmacokinetic parameters of a single oral solifenacin succinate under fasting condition for test and reference preparation were as follows:C max(13.99±3.34)and(13.27±3.20)ng/mL,AUC 0-t(675.60±210.46)and(653.31±238.59)h·ng·mL^-1,AUC 0-∞(728.28±240.20)and(718.14±275.63)h·ng·mL^-1,t max(5.00±1.41)h and(4.98±1.07)h,t 1/2(39.19±9.29)and(42.44±12.66)h.The relative bioavailability was 105.06%for AUC 0-t,104.07%for AUC 0-∞.The main pharmacokinetic parameters of a single oral solifenacin succinate under fed condition for test and reference preparation were as follows:C max(15.65±5.30),(15.02±4.42)ng/mL;AUC 0-t(808.85±271.19),(793.76±256.78)h·ng·mL^-1;AUC 0-∞(917.02±347.82),(875.49±310.77)h·ng·mL^-1.t max(4.29±1.48)h and(5.69±4.10)h,t 1/2(49.47±20.08)and(45.29±12.24)h.The relative bioavailability was 100.91%for AUC 0-t,102.97%for AUC 0-∞.The 90%confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters C max,AUC 0-t,AUC 0-∞of the two preparations under fasting/feding conditions were all within 80%-125%.CONCLUSION:The test and reference preparation of solifenacin succinate tablets are bioequivalent under fasting and fed conditions.