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Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental murine tuberculosis: (1). A study on the efficacy of short course treatment with the intratracheal and intravenous infection model

, : Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental murine tuberculosis: (1). A study on the efficacy of short course treatment with the intratracheal and intravenous infection model. Kekkaku 73(2): 53-64

This study aims to compare in vivo activity of benzoxazinorifamycin KRM-1648 (KRM) with those rifampicin (RFP) and rifabutin (RBT) against experimental murine tuberculosis. Mice were infected with Mycobacterium tuberculosis or M. bovis by the intratracheal (i.t.) or intravenous (i.v.) routes, and treated for 10 days with various doses of each drug starting from the 9th or 11th day after the TB-infection. (A) A rapid test for in vivo evaluation of three rifamycins was conducted by examining the survival days of treated mice infected with 106 cfu of M. bovis Ravenel. Mice treated with KRM exhibited 2.13.7 times longer survival times, in comparison with those treated with RFP or RBT. (B) In the i.t.-model of M. bovis Ravenel infection, three rifamycin derivatives gave "distinctive dose-response curves" in the correlation of dose sizes with the mean survival times or "log10CFU/lungs reductions". (C) In M. tuberculosis Kurono infection models, the ranking of the anti-TB activity of the three rifamycins in each organ was as follows: i.t.-and i.v.-lungs: KRM >> RFP not equal to RBT, i.v.-spleen: KRM not equal to RBT > RFP, i.v.-liver: KRM not equal to RBT > RFP. (D) Based on the results of "log10CFU reduction" in different organs in M. tuberculosis Kurono infection models, "characteristic in vivo activity patterns of each rifamycin" were obtained. (E) The therapeutic efficacy of KRM in lungs was greater than in spleen and liver with any dose. In contrast, RBT exhibited more remarkable in vivo activity in the spleen and liver than in lungs. The prominent in vivo activity of KRM may allow small dose for effective therapy; 1/3 dose or less in comparison with those of RFP or RBT, or intermittent therapy of tuberculosis.


PMID: 9545697

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