吲达帕胺片的药动学和生物等效性研究

目的:评价两种吲达帕胺片剂在中国健康受试者中的药动学特征和生物等效性。方法:采用单剂量、随机、开放、两制剂、两周期、双交叉的试验设计。入组28例健康受试者，随机分成2组，在空腹状态下分别给予1片受试制剂（吲达帕胺片，2.5 mg/片）或参比制剂(纳催离，2.5 mg/片)。在给药前和给药后的72 h内共采集17个血样，全血充分混匀分装后存于-80 ℃冰箱储存。采用液相色谱-串联质谱（LC-MS/MS）法测定人全血中吲达帕胺的浓度。绘制药时曲线，进行药动学参数计算和生物等效性评价。试验期间，通过测量生命体征、体格检查、实验室检查进行安全性评估。结果:28例受试者全部完成试验。受试制剂和参比制剂Cmax、AUC0-t和AUC0-∞的几何均值比的90%置信区间分别为104.94%～119.90%、98.90%～106.34%和98.59%～104.40%，均在80.00%～125.00%的生物等效性范围内。试验过程中，共4例受试者报告了4例轻度不良事件，未发生严重不良事件。结论:健康受试者在空腹状态下单次口服两种吲达帕胺片剂均安全性良好，且两种制剂具有生物等效性。

Pharmacokinetics and bioequivalence study of indapamide tablets

AIM: To evaluate the pharmacokinetics and bioequivalence of 2 indapamide tablets in Chinese healthy subjects. METHODS: A single dose, randomized, open label, two- formulation, two-period crossover design was used. A total of 28 healthy subjects were randomly divided into 2 groups and given 1 tablet of test formulation (indapamide tablet, 2.5 mg/ tablet) or reference formulation (Natrilix, 2.5 mg/tablet) on fasted state. A total of 17 blood samples were collected before and within 72 h after administration, and the whole blood was fully mixed and packaged and stored in the refrigerator at -80 ℃ for storage. The indapamide concentration in human whole blood was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated and the bioequivalence was evaluated. During the study period, vital sign, physical examination and laboratory test were measured after administration for safety assessment. RESULTS:All 28 subjects completed the test. The 90% confidence intervals of the geometric mean ratios of the tested and reference preparations Cmax, AUC0-t and AUC0-∞ were 104.94%-119.90%, 98.90%-106.34% and 98.59%-104.40%, respectively, all of which were within the bioequivalence range of 80.00%-125.00%. During the study, a total of 4 subjects reported 4 mild adverse events and no serious adverse events. CONCLUSION: Two indapamide tablets were safe and bioequivalent in the empty stomach of healthy subjects.