国产含利福平复方制剂药效学及药动学研究

Pharmacodynamics and Pharmacokinetics of Domestic Compound Rifamcicin

目的:研究国产含利福平两药复方制剂的药效学和药物动力学,评价其抗结核作用及产品质量。方法:采用试管二倍稀释法测定最低抑菌浓度,以半数动物存活时间为指标比较药物对实验性结核病的疗效。高效液相色谱法测定健康志愿者口服同剂量国产复方制剂中的利福平及利福平胶囊的血药浓度,求出其中利福平的主要药动学参数及相对生物利用度,并用双单侧t检验分析生物等效性。结果:复方制剂各成分对结核分枝杆菌的MIC均低于单独应用时各自的MIC;对小鼠试验性结核病均显著优于两者相应剂量单独应用的效果,与国外相应产品rifinah(卫非宁)比较未见显著性差异;复方制剂中的利福平与利福平胶囊的主要药动学参数t_(1/2),C_(max),AUC,t_(max)未见显著性差异,相对生物利用度生物等效性检验合格。结论:两药复合剂的抗结核作用具有协同作用;国产与进口片剂的药效学未见显著性差异;国产片中的利福平生物利用度合格。

Objective： To study the pharmacodynamics and pharmacokinetics of domestic compound of antituberculosis drug, assess its quality and activity against Mycobacterium tuberculosis both in vitro and in vivo. Method ： The MIC was determined by the tube doubling dilution method, and the effect of the drugs was assessed by half survival time of the mice. A single oral dose of domestic compound rifamcipin and rifamcipin capsule were given to two groups of healthy volunteers respectively, and rifamcipin concentration in se- rum was determined by HPLC. The pharmacokinetic parameters and relative bioavailability were calculated. Result： The MIC of each composition in the compound （INH, RFP） against Mycobacterium tuberculosis was found lower than that of each composition used by single-dose. In a murine tuberculosis model, the antituberculosis activity of this compound was superior to two of them used alone in same dose. Compared with imported drug, the Relater, no significant difference was found; The main parameters of pharmacokinetics of domestic compound rifamcipin and rifamcipin capsule, t1/2, C AUC, tmax, were not significantly different. The results of the statistical analysis showed that the two formations were bioequivalent. Conclusion： Two composition in the compound drug has synergistic activity, and bioavailability of rifamcipin in domestic compound rifamcipin was qualified.