Ji B, Perani E G, Petinon C, Grosset J H
Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Int J Lepr Other Mycobact Dis. 1992 Dec;60(4):556-61.
The bactericidal activities against Mycobacterium leprae of single or multiple doses of various combinations of new antileprosy drugs [minocycline (MINO), clarithromycin (CLARI), ofloxacin (OFLO), and sparfloxacin (SPFX)] and/or rifampin (RMP) were titrated in immunocompetent mice by the proportional bactericidal method. Drugs were administered by gavage at the following dosages (mg/kg) per dose: RMP 10, MINO 25, CLARI 100, OFLO 150, and SPFX 50. All 15 regimens exerted significant bactericidal activities, at least 96% of viables were killed. The activity of a single dose MINO + CLARI was only slightly inferior to that of RMP, and the activities of a single dose OFLO/SPFX + MINO + CLARI were similar to that of RMP. This suggests that either MINO + CLARI or OFLO/SPFX + MINO + CLARI may be administered once monthly together with RMP 600 mg for the treatment of multibacillary (MB) leprosy, and monthly administration of MINO + CLARI or OFLO/SPFX + MINO + CLARI may also be employed for the treatment of RMP-resistant MB leprosy. Because the killing effects of multiple doses of the combinations were so powerful, comparison of the bactericidal activities of these regimens was beyond the sensitivity of the immunocompetent mouse model, and are being tested in the nude mouse model. Although SPFX is more active against M. leprae than OFLO on a weight-to-weight basis, when both drugs were administered in mice at dosages equivalent to clinically tolerated dosages in humans, SPFX did not show more superiority than OFLO, and its real advantage over OFLO in the treatment of leprosy remains unclear.
通过比例杀菌法在免疫功能正常的小鼠中滴定了新抗麻风病药物[米诺环素（MINO）、克拉霉素（CLARI）、氧氟沙星（OFLO）和司帕沙星（SPFX）]和/或利福平（RMP）的单剂量或多剂量各种组合对麻风分枝杆菌的杀菌活性。药物通过灌胃给药，每剂量的剂量如下（mg/kg）：RMP 10、MINO 25、CLARI 100、OFLO 150和SPFX 50。所有15种方案均具有显著的杀菌活性，至少96%的活菌被杀死。单剂量MINO + CLARI的活性仅略低于RMP，单剂量OFLO/SPFX + MINO + CLARI的活性与RMP相似。这表明MINO + CLARI或OFLO/SPFX + MINO + CLARI可与600 mg RMP一起每月给药一次，用于治疗多菌型（MB）麻风病，每月给予MINO + CLARI或OFLO/SPFX + MINO + CLARI也可用于治疗耐RMP的MB麻风病。由于多剂量组合的杀伤作用非常强大，这些方案杀菌活性的比较超出了免疫功能正常小鼠模型的灵敏度，正在裸鼠模型中进行测试。尽管在重量对重量的基础上，SPFX对麻风分枝杆菌的活性比OFLO更强，但当两种药物在小鼠中以相当于人类临床耐受剂量给药时，SPFX并未显示出比OFLO更具优势，其在麻风病治疗中相对于OFLO的真正优势仍不清楚。
