健康人体内替硝唑片的药代动力学及生物等效性研究

目的研究替硝唑片在健康人体内的相对生物利用度和生物等效性。方法20名健康成年男性志愿者采用随机分组自身交叉试验设计,单剂量口服1.0g替硝唑片后,用高效液相色谱法测定血浆中药物浓度。结果替硝唑在0.208～41.6μg/ml浓度范围内线性良好(r=0.99975),平均回收率98.6%～99.6%,日内和日间标准误(sx)均<10.0%。替硝唑试验制剂和参比制剂的主要药代动力学参数:峰时(Tmax)(:1.5±0.8)和(1.5±1.3)h;峰浓度(Cmax):(20±3)和(21±3)μg/ml;曲线下面积(AUC)0￣60h:(390±55)和(391±48)mg·L-1·h;AUC0￣∞:(427±79)和(424±59)mg·L-1·h;T1/2:(16.6±2.8)和(16.1±1.9)h,以AUC0￣60h计算的受体制剂的相对生物利用度为(100±6)%。结论建立的分析方法准确灵敏,统计学分析表明两种制剂生物等效。

Pharmacokinefics and bioequivalence study of tinidazole tablets in Chinese healthy volunteers

Objective To study the relative bioavailability and bioequivalence of tinidazole tablets (test) to the normal tablets (reference) in Chinese healthy volunteers. Methods Twenty male healthy volunteers were randomized to receive a single crossover oral dose of 1000 mg test tablets or reference tablets.The plasma concentration of tinidazole was determined by high-performance liquid chromatograply(HPLC). Results The method was linear in the 0.208～41.6 μg/ml concentration range(r=0.999 75);the mean recovery was 98.6%～99.6%;The inter-day sx and intra-day sx were less 10%.The main pharmacokinetic parameters without significant difference between test and reference tinidazole tablets were as follows:The inter-day sx and intra-day sx were less 10%;Tmax:(1.5±0.8) vs (1.5±1.3)h;Cmax:(20±3) vs (21±3)mg/L,AUC0~60 h:(390±55) vs (391±48)mg·L-1·h;AUC0~∞:(427±79) vs (424±59)mg·L-1·h;T1/2:(16.6±2.8)vs(16.1±1.9)h;F0~24 h was(100±6)%.The variance analysis and two-one sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax. Conclusion The assay is sensitive,accurate.The test tinidazole tablets is bioequivalent to the reference tablets.