Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, China.
Jangsu Sinomune Pharmaceutical Company Limited, Jiangsu, China.
Clin Pharmacol Drug Dev. 2021 May;10(5):535-541. doi: 10.1002/cpdd.864. Epub 2020 Aug 7.
The purpose of this study was to evaluate the bioequivalence of a generic immediate-release tofacitinib tablet versus a brand-named immediate-release tofacitinib tablet under fasting and fed conditions, and the food effect on pharmacokinetic profiles of the both formulations. This randomized, open-label, 2-period, crossover, bioequivalence study included 52 healthy Chinese subjects (fasting cohort: n = 26; fed cohort: n = 26). The subjects were assigned to receive a single 5-mg dose of generic or brand-named tofacitinib. Blood samples were collected at predosing and up to 14 hours after dosing. Tofacitinib concentrations in plasma were analyzed by high-performance liquid chromatography-tandem mass spectrometry. Safety was monitored. There were no significant differences in maximum plasma concentration, area under the plasma concentration-time curve from time zero to time t (AUC ), AUC from time zero to infinity (AUC ) and terminal elimination half-life between the test and reference formulations (all P > .05); high-fat food had no significant effect on AUC , AUC or terminal elimination half-life of immediate-release tofacitinib tablets (all P > .05). The 90% confidence intervals of the test/reference ratios of log-transformed maximum plasma concentration, AUC , and AUC were within the range of 80% to 125% under both fasting and fed conditions. No serious adverse events were reported. The 2 formulations of immediate-release tofacitinib tablets are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. Food had no clinically relevant effects on drug exposure of tofacitinib.
本研究旨在评估空腹和进食条件下，一种通用的即刻释放托法替布片剂与一种品牌的即刻释放托法替布片剂的生物等效性，以及两种制剂的药代动力学特征的食物效应。这是一项随机、开放标签、2 期、交叉、生物等效性研究，纳入了 52 名健康的中国受试者（禁食组：n = 26；进食组：n = 26）。受试者被分配接受单次 5mg 剂量的通用或品牌托法替布。在给药前和给药后 14 小时内采集血样。采用高效液相色谱-串联质谱法分析血浆中的托法替布浓度。监测安全性。试验制剂和参比制剂的最大血浆浓度、从零时间到时间 t 的血浆浓度-时间曲线下面积（AUC ）、从零时间到无穷大的 AUC （AUC ）和终末消除半衰期均无显著差异（均 P >.05）；高脂肪饮食对即刻释放托法替布片剂的 AUC 、 AUC 或终末消除半衰期无显著影响（均 P >.05）。在禁食和进食条件下，试验/参比比值的对数转换最大血浆浓度、AUC 和 AUC 的 90%置信区间均在 80%至 125%范围内。未报告严重不良事件。在健康的中国志愿者中，即刻释放托法替布片剂的两种制剂在空腹和进食条件下均具有生物等效性和良好的耐受性。食物对托法替布的药物暴露没有临床相关影响。
