Bactericidal action at low doses of a new rifamycin derivative, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl) benzoxazinorifamycin (KRM-1648) on Mycobacterium leprae inoculated into footpads of nude mice.
Among a series of newly-synthesized benzoxazinorifamycins, 2 of the 3'-hydroxy-5'-(4-alkyl-1-piperazinyl) derivatives, named KRM-1648 and KRM-2312, whose respective alkyl residues are isobutyl and isopropyl, were examined for efficacy against nude mouse-model leprosy. KRM-1648 completely inhibited the growth of leprosy bacilli inoculated into nude mouse footpads, even 6 months after the medication had been stopped, when given orally at a daily dose of 0.6 mg/kg, 5 or 6 times weekly, during 3-5 months postinoculation. In comparison, the growth inhibition by KRM-2312 was incomplete under the same conditions, though it was still stronger than that by rifampicin. Complete growth inhibition by KRM-1648 was also observed when it was given orally at a dose of 1 or 3 mg/kg twice weekly during the same period. In contrast, the growth inhibition by rifampicin was only slight at 1 mg/kg and partial at 3 mg/kg under the same condition.
Gidoh
M
M
National Institute for Leprosy Research, Tokyo, Japan.
Tsutsumi
S
S
Yamane
T
T
Yamashita
K
K
Hosoe
K
K
Hidaka
T
T
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009166:Mycobacterium leprae / Q000187:drug effects / Q000254:growth & development*; D012293:Rifampin / Q000494:pharmacology; D012294:Rifamycins / Q000494:pharmacology*
D000904:Antibiotics, Antitubercular; D012294:Rifamycins; C068980:KRM 1648; D012293:Rifampin