In vivo antileprosy activity of the newly synthesized benzoxazinorifamycin, KRM-1648.
The in vivo anti-Mycobacterium leprae activity of the newly synthesized benzoxazinorifamycin, KRM-1648, was studied. KRM-1648 was given orally to athymic nude mice, infected subcutaneously with M. leprae in the hindfoot pad, at doses between 0.001 and 0.01 mg of the drug/mouse/day six times per week, from day 31 to day 80. KRM-1648 administration markedly suppressed bacterial growth in the foot pads for 360 days. KRM-1648 given daily at the dose of 0.01 mg/mouse elicited a 2-4-log decrease in the number of acid-fast bacilli. The therapeutic effects of KRM-1648 were significantly higher than that of rifampin when both drugs were given in the same dosage. Moreover, when mice were fed a KRM-1648-containing diet (0.00004%-0.0004%), the drug displayed an even higher efficacy against M. leprae infection, causing an almost 4-log decrease in the number of leprosy bacilli in the infected foot pad compared to untreated controls.
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
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Tomioka
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Saito
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007917:Leprostatic Agents / Q000627:therapeutic use*; D007918:Leprosy / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000187:drug effects / Q000302:isolation & purification; D012293:Rifampin / Q000008:administration & dosage; D012294:Rifamycins / Q000627:therapeutic use*
D007917:Leprostatic Agents; D012294:Rifamycins; C068980:KRM 1648; D012293:Rifampin