Grosset J H, Guelpa-Lauras C C, Perani E G, Beoletto C
Département de Bactériologie-Virologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Int J Lepr Other Mycobact Dis. 1988 Jun;56(2):259-64.
Mice inoculated with 4800 Mycobacterium leprae in the left hind foot pad were treated from day 62 to day 150 after infection with 50 mg or 150 mg of ofloxacin per kg body weight, 150 mg pefloxacin per kg, or 50 mg prothionamide per kg. These drugs were administered by esophageal cannula 5 days weekly with dapsone (0.01 g per 100 g diet). Multiplication of M. leprae in the treated and in untreated control mice was assessed by monthly harvests. The treatment of mice with the smaller dosage ofloxacin, with pefloxacin, prothionamide, or dapsone uniformly resulted in a delay of multiplication of 4 months, compared to the multiplication of M. leprae in the untreated controls. The delay of multiplication (4 months) being 1 month longer than the duration of drug administration (3 months), all of the treatments may be considered as bacteriopausal or moderately bactericidal. In contast with these results, treatment of mice with 150 mg ofloxacin per kg resulted in no growth of the organisms whatever as late as 18 months after inoculation, strongly suggesting that, in that dosage, ofloxacin had killed all of the M. leprae. Such a profound killing activity has been observed only with rifampin. Although the pharmacokinetic characteristics of ofloxacin are different in man from those in the mouse, the daily dosage of 150 mg ofloxacin per kg body weight in the mouse is equivalent to 400 mg per day in man which is the usual therapeutic dosage; thus, the results obtained in the mouse may be extrapolated to man. Therefore, ofloxacin appears a very promising drug for the chemotherapy of leprosy.
给左后足垫接种4800个麻风分枝杆菌的小鼠，在感染后第62天至第150天，用每千克体重50毫克或150毫克氧氟沙星、每千克150毫克培氟沙星或每千克50毫克丙硫异烟胺进行治疗。这些药物通过食管插管每周给药5天，同时给予氨苯砜（每100克饮食0.01克）。通过每月采集样本评估治疗组和未治疗对照组小鼠体内麻风分枝杆菌的繁殖情况。与未治疗对照组中麻风分枝杆菌的繁殖相比，用较小剂量氧氟沙星、培氟沙星、丙硫异烟胺或氨苯砜治疗小鼠均使繁殖延迟4个月。繁殖延迟（4个月）比给药持续时间（3个月）长1个月，所有这些治疗都可被视为抑菌或中度杀菌。与这些结果形成对比的是，每千克体重用150毫克氧氟沙星治疗小鼠，直到接种后18个月细菌都没有生长，这强烈表明，在该剂量下，氧氟沙星已杀死了所有麻风分枝杆菌。只有利福平观察到过如此强大的杀菌活性。虽然氧氟沙星在人体内的药代动力学特征与小鼠不同，但小鼠每千克体重每天150毫克氧氟沙星的剂量相当于人每天400毫克，这是通常的治疗剂量；因此，在小鼠身上获得的结果可以外推到人类。所以，氧氟沙星似乎是一种非常有前景的麻风病化疗药物。
