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利福喷汀-莫西沙星-米诺环素联合用药(PMM)治疗麻风病

Combination of rifapentine-moxifloxacin-minocycline (PMM) for the treatment of leprosy.

作者信息

Ji B, Grosset J

机构信息

Faculté de Médicine Pitié-Salpêtrière, Paris, France.

出版信息

Lepr Rev. 2000 Dec;71 Suppl:S81-7. doi: 10.5935/0305-7518.20000074.

Abstract

To further the development of a multidrug regimen for treatment of leprosy that is suitable for monthly administration and fully supervisable, the bactericidal activities against Mycobacterium leprae of HMR 3647 (HMR), moxifloxacin (MXFX) and rifapentine (RPT) were measured by the proportional bactericide technique in the mouse footpad system, and compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO) and rifampicin (RMP). Administered in five daily doses of 100 mg per kg body weight, HMR appeared slightly more bactericidal than CLARI, but the difference did not attain statistical significance. Administered as single doses, MXFX in a dosage of 150 mg per kg was more active than OFLO in the same dosage, and displayed the same level of activity as RMP in a dosage of 10 mg per kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT in a dosage of 10 mg per kg was more bactericidal than RMP administered in the same dosage, and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable M. leprae, and was slightly more bactericidal than was RPT alone, indicating that the combination PMM showed an additive effect against M. leprae. These promising results justify a clinical trial among lepromatous patients, in which MM is being compared with OM, and PMM with ROM, in terms of efficacy and tolerance.

摘要

为进一步研发适合每月给药且可全程监督的麻风病多药治疗方案,采用小鼠足垫系统中的比例杀菌技术测定了HMR 3647(HMR)、莫西沙星(MXFX)和利福喷汀(RPT)对麻风分枝杆菌的杀菌活性,并与已有的抗麻风病药物克拉霉素(CLARI)、氧氟沙星(OFLO)和利福平(RMP)进行比较。以每日5次、每次每千克体重100 mg的剂量给药时,HMR的杀菌效果似乎略优于CLARI,但差异无统计学意义。单剂量给药时,每千克体重150 mg的MXFX比相同剂量的OFLO活性更高,且与每千克体重10 mg的RMP活性相当;MXFX-米诺环素(MINO)(MM)组合比OFLO-MINO(OM)组合杀菌效果更好;每千克体重10 mg的RPT比相同剂量的RMP杀菌效果更好,甚至比RMP-OFLO-MINO(ROM)组合更具活性;RPT-MXFX-MINO(PMM)组合可杀灭99.9%的存活麻风分枝杆菌,且杀菌效果略优于单独使用RPT,表明PMM组合对麻风分枝杆菌具有相加作用。这些有前景的结果为在瘤型麻风患者中开展临床试验提供了依据,该试验将比较MM与OM、PMM与ROM在疗效和耐受性方面的差异。

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