国产抗结核固定剂量复合剂的药效学和药代动力学研究

目的 研究国产固定剂量复合剂的药效学和药代动力学，评价其抗结核作用及产品质量。方法 采用二倍稀释法测定最低抑菌浓度（MIC），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及进口三药复方片剂（卫非特）的血药浓度，求出各组分的主要药代动力学参数及相对生物利用度，并用双单侧t检验分析药物等效性。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三者相应剂量单独应用的效果，与国外相应产品卫非特比较未见显著性；国产与进口片剂的主要药代动力学参数t1/2、Cmax、AUC、tmax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 三药复方的抗结核作用具有协同作用；国产与进口片剂为等效制剂。

Pharmacodynamics and pharmacokinetics of domestic fixed-dose combination of antituberculosis drugs

Objective To study the pharmacodynamics and pharmacokinetics of domestic fixed dose of antituberculosis drugs,and to evaluate its quality and activity against Mycobacterium tuberculosis both in vitro and in vivo. Methods 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 and imported fixed dose combination of antituberculosis drugs was given to healthy volunteers, and the drug concentration in serum was determined by HPLC. The pharmacokinetic parameters and the relative bioavailability were calculated. Results The MIC of each composition in the compound (INH, RFP, PZA) against Mycobacterium tuberculosis was lower than that of each composition used by single dose. In a murine tuberculosis model, the antituberculosis activity of this compound drug was superior to that of each agent used alone with the same dose. No significant difference was found as compared to the imported drug, Refater; The major pharmacokinetic parameters of the domestic and the imported drugs, t 1/2 , C max , AUC, and t max , were not significantly different. Statistical analysis showed the two formulations were bioequivalent.Conclusion The three compositions in the combination had synergistic effect, and the domestic and the imported drugs were bioequivalent.