来氟米特片在健康中国受试者的生物等效性研究

目的:评价健康成年受试者给予来氟米特片受试制剂和参比制剂(ARAVA?)在空腹和餐后状态时的生物等效性和安全性。方法:采用单中心、随机、开放、两制剂、单剂量、单周期、平行给药的试验设计,健康受试者分别空腹(50例)和餐后(50例)服用20 mg来氟米特片参比制剂或受试制剂,采用液相色谱-串联质谱法(LC-MS/MS)测定血浆特立氟胺浓度。使用Phoenix WinNonlin 8.3软件计算药动学参数,进行等效性评价。结果:空腹组和餐后组,受试制剂和参比制剂的C_max和AUC_{0-72 h}的几何均值比值(受试制剂/参比制剂)的90%置信区间均介于80%~125%的等效范围内。试验共发生117例次(空腹68例次,餐后49例次)与药物有关的不良事件,未发生严重不良事件。结论:受试制剂与参比制剂在空腹及餐后服用的情况下生物等效,安全性良好。

Bioequivalence evaluation of leflunomide tablets in healthy Chinese subjects

OBJECTIVE To evaluate the bioequivalence and safety of leflunomide tablets test product and reference product (ARAVA?) in healthy adult subjects under fasting and fed conditions.METHODS A single-center, randomized, open-label, two-treatment, single-dose, single-period and parallel-dose study design was used to determine teriflunomide plasma concentration by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in healthy subjects receiving 20 mg of leflunomide tablets reference or test product under fasting (50 subjects) and fed (another 50 subjects) conditions. The pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.3 software for the equivalence evaluation.RESULTS The 90% confidence intervals of the geometric mean ratio (test/reference) for C_max and AUC_{0-72 h} for the test and reference products were within the equivalence range of 80%-125% for both the fasting and fed groups. A total of 117 drug-related adverse events (68 under fasting condution and 49 under fed condition) occurred in the study, and no serious adverse event occurred.CONCLUSION The test product and the reference product are bioequivalent under fasting and fed conditions both with good safety.