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利福平和吡嗪酰胺,与INH、链霉素或乙胺丁醇一道,构成了对结核病治疗中所提倡的药物方案中的一个重要部分。国际防痨和肺病联合会业已建议采用这两个药物作为结核病短程化学治疗的一部分。因此,本研究承担起评价两药同时给予时,吡嗪酰胺对利福平动力学的影响。 在一项随机化的、交迭法的、单一剂量的研究中,未经治疗的16名肺结核病人,经过过夜的禁食后,给予利福平450mg+INH 300mg(研究A组)或利福平450mg+INH300mg+吡嗪酰胺1500mg(研究B组)。为检测血清中利福平于0.5、2、4、6、和8小时进行血样采集。各种药物动力学的参数(利福平的Cmax、Tmax、t1/2、Kel、血浆浓度-时间曲线下的面积(AUC)、Vd和Cpl)均予以计算。 已经观察到,研究A组利福平的浓度于6小时(P<0.01)、8小时(P<0.05),与研究B组相反,明显地较高,而于0.5、2和4小时的血清中利福平浓度没有显著差异。AUC和Cpl也有显著差异。与研究B组相比,研究A组的AUC较高(P<0.05),而Cpl较低(P<0.02)。 从以上数据可见,在用利福平治疗的病人中合并给予吡嗪酰胺,利福平的AUC减少,而它的廓清率增加。
Rifampin and pyrazinamide, together with INH, streptomycin or ethambutol, constitute an important part of the drug regimen advocated in the treatment of tuberculosis. The International Federation of Tuberculosis and Lung Disease has recommended the use of both drugs as part of TB TB treatment. Therefore, this study assumed the evaluation of the two drugs at the same time, pyrazinamide on rifampin kinetics. In a randomized, crossover, single-dose study, untreated 16 tuberculosis patients received either rifampicin 450 mg + INH 300 mg (Study Group A) or Rifabin after overnight fasting Flat 450mg + INH 300mg + Pyrazinamide 1500mg (Study Group B). Blood samples were taken for serum rifampicin at 0.5, 2, 4, 6, and 8 hours. Various pharmacokinetic parameters (rifampicin Cmax, Tmax, t1 / 2, Kel, area under the plasma concentration-time curve (AUC), Vd and Cpl) were calculated. It has been observed that concentrations of rifampicin in study group A were significantly higher at 6 hours (P <0.01) and 8 hours (P <0.05), as opposed to study group B, whereas serum concentrations at 0.5, 2 and 4 hours There was no significant difference in rifampicin concentrations. AUC and Cpl also have significant differences. Compared with study group B, study group A had higher AUC (P <0.05) and lower Cpl (P <0.02). As can be seen from the above data, in the patients treated with rifampicin given pyrazinamide, rifampin AUC decreased, and its clearance rate increased.