替硝唑片在中国健康受试者中的生物等效性研究

Bioequivalence of tinidazole tablets in healthy Chinese volunteers

目的评价2种替硝唑片在中国健康受试者中的生物等效性及安全性。方法按单中心、随机、开放、单次给药、两序列、两制剂、两周期、交叉试验研究设计方法,在餐后条件下,共入组24例健康受试者,随机交叉单次口服受试制剂和参比制剂各500 mg,用HPLC-MS/MS法来测定受试者血浆中替硝唑浓度,用Phoenix WinNonlin(7.0版本)软件以计算替硝唑药代动力学参数,并进行生物等效性评价。结果受试者在服用受试制剂和参比制剂后,其血浆中替硝唑主要药代动力学参数如下:Cmax分别为(1.21×10^4±2048.85)和(1.20×10^4±2132.68) ng·mL^-1;AUC0-t分别为(24.93×10^4±3.62×10^4)和(24.55×10^4±3.06×10^4) ng·h·mL^-1;AUC0-∞分别为(25.96×10^4±3.91×10^4)和(25.60×10^4±3.27×10^4) ng·h·mL^-1。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后的90%可信区间为96.11%~106.45%,99.41%~103.12%,99.25%~103.02%。结论 2种替硝唑片在中国健康受试者中具有生物等效性。

Objective To evaluate the bioequivalence of two kinds of tinidazole tablets in China healthy subjects. Methods This was a single-center, randomized, open-label, single-dose, two-period, cross-over pharmacokinetic study. A total of 24 subjects in a fed state were given single oral dose of test and reference preparation of tinidazole tablets(each 500 mg), respectively. The concentration of tinidazole in human plasma was measured by HPLC-MS/MS. Main pharmacokinetic parameters were calculated by using Phoenix WinNonlin(V7.0) software. Results The main pharmacokinetic parameters of tinidazole of the test and reference preparations were as follows: the fed state Cmax were(1.21×10^4±2048.85) and(1.20×10^4±2132.68) ng·mL^-1;AUC0-t were(24.93×10^4±3.62×10^4) and(24.55×10^4±3.06×10^4) ng·h·mL^-1;AUC0-∞ were(25.96×10^4±3.91×10^4) and(25.60×10^4±3.27×10^4) ng·h·mL^-1. The 90% confidential interval of Cmax, AUC0-t and AUC0-∞ of tested formulation in the fed state were 96.11%-106.45%, 99.41%-103.12%,99.25%-103.02%. Conclusion Two kinds of tinidazole tablets are determined to be bioequivalent.