替格瑞洛片在中国健康受试者中的生物等效性研究

Bioequivalence of tegrilol tablets in Chinese healthy subjects

目的研究替格瑞洛片在中国健康人体内的生物等效性。方法空腹试验52例、餐后试验52例健康受试者按双周期、自身交叉设计、单剂量口服替格瑞洛片受试制剂或参比制剂90 mg,用液相色谱-质谱法测定血浆中替格瑞洛和代谢产物AR-C124910XX的血药浓度,用WinNonlin 6.3软件计算药代动力学参数及相对生物利用度,判定两制剂是否等效。结果空腹试验受试制剂和参比制剂替格瑞洛C_(max)分别为(605.60±196.61)和(609.10±235.74)ng·mL^(-1),AR-C124910XX C_(max)分别为(197.73±61.27)和(194.62±59.12)ng·mL^(-1),替格瑞洛AUC_(0-t)分别为(3374.33±1240.33)和(3261.81±1232.11)h·ng·mL^(-1),AR-C124910XX AUC_(0-t)分别为(1714.76±604.04)和(1691.09±600.45)h·ng·mL^(-1),替格瑞洛AUC_(0-∞)分别为(3418.44±1257.44)和(3305.66±1252.88)h·ng·mL^(-1),AR-C124910XX AUC_(0-∞)分别为(1768.78±627.67)和(1740.08±623.40)h·ng·mL^(-1)。餐后试验受试制剂和参比制剂替格瑞洛C_(max)分别为(489.10±139.26)和(517.10±148.91)ng·mL^(-1),AR-C124910XXC_(max)分别为(108.06±37.97)和(113.93±34.96)ng·mL^(-1),替格瑞洛AUC_(0-t)分别为(4047.99±1085.56)和(4083.91±1104.30)h·ng·mL^(-1),AR-C124910XX AUC_(0-t)分别为(1479.49±508.70)和(1506.56±539.16)h·ng·mL^(-1),替格瑞洛AUC_(0-∞)分别为(4123.62±1128.98)和(4158.73±1143.93)h·ng·mL^(-1),AR-C124910XX AUC_(0-∞)分别为(1572.63±565.55)和(1598.42±601.39)h·ng·mL^(-1)。受试制剂与参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%置信区间均完全落在80.00%~125.00%。结论2种替格瑞洛片在中国健康受试者体内具有生物等效性。

Objective To evaluate the bioequivalence of tegrilol tablets in healthy Chinese.Methods Fasting test in 52 subjects,postprandial test in 52 healthy subjects with two cycles,complete repetition,self-cross design,single dose oral ticagrelor tablet test preparation or reference preparation 90 mg,the concentrations of ticagrelor and its metabolite AR-C124910 XX in plasma were determined by liquid chromatography-mass spectrometry.The pharmacokinetic parameters and relative bioavailability were calculated by software WinNonlin 6.3 to determine whether the two preparations were equivalent.Results Under fasting state,the C_(max) of ticagrelor test and reference were(605.60±196.61)and(609.10±235.74)ng·mL^(-1),AUC_(0-t) were(3374.33±1240.33)and(3261.81±1232.11)h·ng·mL^(-1),AUC_(0-∞)were(3418.44±1257.44)and(3305.66±1252.88)h·ng·mL^(-1),respectively;the C_(max) of AR-C124910 XX test and reference were(197.73±61.27)and(194.62±59.12)ng·mL^(-1),AUC_(0-t) were(1714.76±604.04)and(1691.09±600.45)h·ng·mL^(-1),AUC_(0-∞)were(1768.78±627.67)and(1740.08±623.40)h·ng·mL^(-1).The main pharmacokinetic parameters of ticagrelor test and reference under postprandial state were C_(max)(489.10±139.26)and(517.10±148.91)ng·mL^(-1),AUC_(0-t)(4047.99±1085.56)and(4083.91±1104.30)h·ng·mL^(-1),AUC_(0-∞)(4123.62±1128.98)and(4158.73±1143.93)h·ng·mL^(-1),respectively;the main pharmacokinetic parameters of AR-C124910 XX under postprandial state were C_(max)(108.06±37.97)and(113.93±34.96)ng·mL^(-1),AUC_(0-t)(1479.49±508.70)and(1506.56±539.16)h·ng·mL^(-1),AUC_(0-∞)(1572.63±565.55)and(1598.42±601.39)h·ng·mL^(-1).The 90%confidence intervals of C_(max),AUC_(0-t),AUC_(0-∞)geometric mean ratio of test preparation and reference preparation were all within 80.00%-125.00%.Conclusion The two ticagrelor tablets are bioequivalent in healthy Chinese volunteers.