赵伟杰 李惠文 梁桂芳 郭振勇 段连山 (北京市结核病胸部肿瘤研究所 北京 101149)
摘 要 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：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。
关键词 抗结核；利福平；药效学； 药物动力学； 生物利用度
中图分类号：R978.3
文献标识码：A
文章编号：1008-049X(2007)07-0637-04
Pharmacodynamics and Pharmacokinetics of Domestic Compound Rifamcicin
Zhao Weijie，Li Huiwen，Liang Guifang，Guo Zhenyong, Duan Lianshan（Department of Pharmacology, Beijing Institute of Tuberculosis and Thoracic Tumor, Beijing 101149,China）
ABSTRACT 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 serum was determined by HPLC. The pharmacokinetic parameters and relative bioavailability were calculated.Result: The MICof each composition in the compound (INH, RFP) against Mycobacterium tuberculosis was found lower than that of each composition used by singledose. 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 Refater, no significant difference was found; The main parameters of pharmacokinetics of domestic compound rifamcipin and rifamcipin capsule,t1/2,Cmax,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.
KEY WORDS Antituberculosis; Rifamcipin; Pharmacokinetics; Pharmacodynamics; Bioavailability.
参 考 文 献
1 Fox W. Drug combinations and the bioavailability of rifampincin［J］. Tuberculosis, 1990, 71(1):241-245
2 International Union Against Tuberculosis and Lung Disease. Antituberculosis regiment of Treatment of the IUATLD［J］. Bull Int Union Tuberc Lung Dis, 1988, 63(1):60-64
3 World Health Organization Tuberculosis Program. Treatment of tuberculosis: guidelines for national programmes［S］. Geneva：World Health Organization, 1993
4 Pillai G, Fourie PB, Padayatchi N, et al. Recent bioequivalence studies on fixeddose combination antituberculosis drug formulations available on the global market［J］. Int J Tuberc Lung Dis, 1999, 3(11 Suppl 3):309-316
5 Fourie PB, Spinaci S. Structures required, roles and responsibilities in maintaining laboratories for quality assurance of antituberculosis with the IUATLD /WHO statement［J］.Int J Tuberc Lung Dis, 1999,3(11 Suppl 3):368-370
6 Fourie PB. Proposed minimum registration requirements for fixeddose combination antituberculosis drugs［J］. Int J Tuberc Lung Dis, 1999, 3(11 Suppl 3): 362-367
7 Padgaonkar KA, Revankar SN, Bhatt AD，et al. Comparative bioequivalence study of rifampicin and isoniazid combination in healthy volunteers［J］. Int J Tuberc Lung Dis,1999,3(7):627-631
8 Shishoo CJ，Shah SA，Pathod IS，et al. Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose combination(FDC) formulation［J］. Int J Pharm, 2001,228(1-2):53-67
9 Singh S，Mariappan TT，Shankar R，et al. A critical review of the probable reasons for the poor variable bioavailability of rifampicin from antitubercular fixdose combination(FDC) products and the likely solution to the problem［J］. Int J Pharm，2001,228(1-2):5-17
10 A joint statement of the International Union Against Tuberculosis and Lung Disease and the world Health Organization. Assuring bioavailability of fix dose combination of antituberculosis medications［J］. Int J Tuberc Lung Dis,1999，(11 suppl 3):282-283
11 Panchagnula R, Singh I, Kaur KJ, et al. Bioequivalence study of rifampicin in fixeddose combination of rifampicin and isoniazid separate formulations［J］. Methods Find Exp Clin Pharmacol，1999，21(9):625-628
12 谭卫国，程锦泉，吴清芳，等.抗结核固定复合制剂与板式组合药治疗肺结核可行性的对照研究［J］.中国防痨杂志，2005,27(4):209-214 资料来自:中国药师-专业站 |