title: Inhibition of the multiplication of Mycobacterium leprae in nude mice by intermittent administration of a new rifamycin derivative, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) combined with sparfloxacin.
abstract: Inhibition of the multiplication of Mycobacterium leprae in the footpads of nude mice by the oral administration of sparfloxacin, a new quinolone, and 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648), selected from a series of newly synthesized benzoxazinorifamycins, was studied. When the 2 drugs were administered alternately at intervals of 3 or 4 days, (i.e., each drug was administered once weekly), or simultaneously once weekly, between 3 and 5 months after inoculation of nude mice with M. leprae, 10 mg sparfloxacin and 0.6 mg KRM-1648 per kg bodyweight were sufficient to prevent multiplication of the organisms. Only partial inhibition of multiplication was achieved by alternate administration of 5 mg sparfloxacin and 0.3 mg KRM-1648 per kg, as was the case for 20 mg sparfloxacin per kg or 1 mg KRM-1648, each drug administered alone once weekly. The addition to these 2 drugs of dapsone, administered in the diet in a concentration of 0.001 g per 100 g, enhanced their effect. The potential usefulness of multidrug regimens including these compounds is considered.
authors.affiliation: National Institute for Leprosy Research, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Gidoh
authors.forename: G
authors.initials: G
authors.lastname: Matsuki
authors.forename: S
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Hidaka
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003622:Dapsone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage*; D005260:Female; D024841:Fluoroquinolones; D007917:Leprostatic Agents / Q000008:administration & dosage*; D007918:Leprosy / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development; D015363:Quinolones / Q000008:administration & dosage; D012294:Rifamycins / Q000008:administration & dosage
chemical_list: D024841:Fluoroquinolones; D007917:Leprostatic Agents; D015363:Quinolones; D012294:Rifamycins; C068980:KRM 1648; D003622:Dapsone; C061363:sparfloxacin