Gidoh M, Tsutsumi S, Yamane T, Yamashita K, Hosoe K, Hidaka T
National Institute for Leprosy Research, Tokyo, Japan.
Lepr Rev. 1992 Dec;63(4):319-28.
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.
在一系列新合成的苯并恶嗪利福霉素中，对3'-羟基-5'-(4-烷基-1-哌嗪基)衍生物中的2种进行了裸鼠模型麻风病疗效研究，这2种衍生物分别名为KRM-1648和KRM-2312，其烷基残基分别为异丁基和异丙基。KRM-1648在接种后3至5个月内，以0.6毫克/千克的日剂量口服，每周5或6次，完全抑制了接种到裸鼠脚垫中的麻风杆菌生长，甚至在停药6个月后仍有抑制作用。相比之下，在相同条件下，KRM-2312的生长抑制作用不完全，尽管仍比利福平强。在同一时期，当KRM-1648以1或3毫克/千克的剂量每周口服两次时，也观察到了完全的生长抑制作用。相比之下，在相同条件下，利福平在1毫克/千克时生长抑制作用轻微，在3毫克/千克时生长抑制作用不完全。
