异烟肼片空腹单次给药人体生物等效性研究

Bioequivalence study of isoniazid tablets with a single dose fasting administration in healthy volunteers

目的评价中国健康受试者空腹状态下口服异烟肼片的人体生物等效性与安全性。方法本研究为空腹状态下开放、随机、单次给药、两制剂、两序列、两周期、双交叉试验设计,清洗期3 d。30例受试者,随机分为两组(T-R组和R-T组),每组受试者分别交叉口服异烟肼片的受试制剂和参比制剂1片。采用液相色谱-串联质谱(LC-MS/MS)法检测给药后血浆中异烟肼的浓度。运用Phoenix WinNonlin软件(8.0版本)计算主要药代动力学参数。结果受试者空腹单次口服受试制剂与参比制剂后,C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值的比值(受试制剂/参比制剂)分别为95.75%、98.51%、98.89%。其90%置信区间分别为85.23%~107.57%、95.36%~101.77%、95.66%~102.24%,均落在80.00%~125.00%之间。安全性数据显示,不良事件严重程度除2例次为Ⅱ级外,其余均为Ⅰ级,无严重不良事件发生,无导致受试者退出的不良事件。结论受试制剂与参比制剂异烟肼片在空腹状态下药动学评价指标具有生物等效性,且受试者在本试验给药剂量下安全性良好。

Objective To evaluate the bioequivalence and safety of two formulations of 100 mg isoniazid tablets in healthy Chinese subjects under fast conditions.Methods This was a single-center open-label,randomized,single-dose,two formulations,two-sequence,two-periods,two-way crossover bioequivalence study in healthy Chinese subjects under fasting conditions,and the cleaning period is 3 days.30 subjects were randomly divided into two groups(T-R group and R-T group),and each group of subjects were cross-administered the test formulation of isoniazid tablets and reference formulation.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was used to detect the concentration of isoniazid in plasma after administration.Use the Phoenix WinNonlin software to calculate the main pharmacokinetic parameters.Results After subjects took a single oral administration of isoniazid tablet test and reference preparations on an empty stomach,the ratios of geometric mean values of C_(max),AUC_(0-t) and AUC_(0-∞)(test preparation/reference preparation)were 95.75%,98.51% and 98.89% respectively.The 90%CI were 85.23%~107.57%,95.36%~101.77%,95.66%~102.24%,all falling between 80.00%~125.00%.Safety data shows that the severity of adverse events was grade Ⅰ except for 2 cases of grade Ⅱ.No serious adverse events occurred and no adverse events that caused the subject to withdraw.Conclusion The pharmacokinetic evaluation indexes of the test and reference isoniazid tablets are bioequivalent under fasting conditions,and the subjects have good safety at the dose of this test.