国产枸橼酸托法替布片的药动学及生物等效性研究

Pharmacokinetics and Bioequivalence Study of Generic Tofacitinib Citrate Tablets

目的通过探讨2种枸橼酸托法替布片在健康人群中的药动学特征,评价其生物等效性和安全性。方法采用随机、两周期、自身交叉设计,空腹/餐后各纳入36例受试者,每周期分别服用枸橼酸托法替布片(T或R)5 mg各1片,采用液相色谱-串联质谱(LC-MS/MS)法检测血浆中托法替布片的浓度,Phoenix WinNonlin软件进行分析,计算药动学参数,评价其生物等效性。结果受试者单次口服T和R后,空腹组托法替布的主要药动学参数血药峰浓度(C_(max))分别为(57.54±13.95)、(59.17±12.31)ng·mL^(-1);浓度-时间曲线下面积(AUC_(0-t))分别为(143.83±34.58),(142.13±33.00)ng·h·mL^(-1);AUC_(0-∞)分别为(147.39±35.27)、(146.15±34.64)ng·h·mL^(-1);达峰时间(t_(max))均为0.50 h,餐后组托法替布的主要药动学参数C_(max)分别为(57.16±17.56)、(55.19±21.98)ng·mL^(-1);AUC_(0-t)分别为(165.47±41.63)、(162.04±41.84)ng·h·mL^(-1);AUC_(0-∞)分别为(171.88±44.15)、(168.05±44.21)ng·h·mL^(-1);t_(max)均为1.0 h,两制剂空腹组和餐后组C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%置信区间分别为96.35%(90.11%~103.03%)和105.91%(95.20%~117.83%)、101.02%(98.76%~103.34%)和102.23%(99.67%~104.86%)、100.77%(98.53%~103.06%)和102.40%(99.81%~105.06%),均在80.00%~125.00%内。结论2种枸橼酸托法替布片在中国健康人群中生物等效,并且安全性良好。

Objective To assess the pharmacokinetic characteristics of two types of tofacitinib citrate tablets in healthy individuals and evaluate their bioequivalence and safety.Methods A randomized,two-period,self-crossing design was used with 36 subjects in two groups in both fasting and postprandial conditions.Each group received 5 mg tofacatile citrate tablets of either generic tofacitinib citrate tablets(T)or the reference product(R)per period,and the plasma concentration of tofacatile tablets was detected by LC-MS/MS.Phoenix WinNonlin software was used to calculate pharmacokinetic parameters and evaluate its bioequivalence.Results After single oral administration of test and reference preparations,the main pharmacokinetic parameters were as follows:C_(max) values in fasting group were(57.54±13.95)and(59.17±12.31)ng·mL^(-1),respectively;AUC_(0-t) values were(143.83±34.58)and(142.13±33.00)ng·h·mL^(-1),respectively;AUC_(0-∞)values were(147.39±35.27)and(146.15±34.64)ng·h·mL^(-1),respectively;t_(max) was 0.5 h for both;C_(max) values in the postprandial group were(57.16±17.56)and(55.19±21.98)ng·mL^(-1);AUC_(0-t) values were(165.47±41.63)and(162.04±41.84)ng·h·mL^(-1);AUC_(0-∞)values were(171.88±44.15)and(168.05±44.21)ng·h·mL^(-1);The t_(max) was 1.0 h for both.The 90%confidence intervals for the geometric mean ratios of C_(max),AUC_(0-t) and AUC_(0-∞)in fasting group and postprandial group were 96.35%(90.11%-103.03%)and 105.91%(95.20%-117.83%),101.02%(98.76%-103.34%)and 102.23%(99.67%-104.86%),100.77%(98.53%-103.06%)and 102.40%(99.81%-105.06%),all within the range of 80.00%-125.00%.Conclusion Both types of generic tofacitinib citrate tablets are bioequivalent and safe in Chinese healthy individuals.