[In vivo activities of new rifamycin derivatives against mycobacteria]

Abstract

Therapeutic effects of new rifamycin derivatives, 3'-hydroxy-5'-(4-alkylpiperazinyl) benzoxazinorifamycins, KRM 1648, 1657, 1668, 1674 and 2312 (kindly supplied by Kanegafuchi Chem. Ind. Co. Japan), were evaluated on experimental tuberculosis and Mycobacterium avium complex infection in mice. I. Experimental tuberculosis in mice Male ddY mice were inoculated via tail vein with ca. 1 x 10(9) CFU of M. tuberculosis H37Rv suspended in 0.2 ml medium. Treatment of the mice with the new rifamycin derivatives or rifampicin (RFP: as a control drug) was performed by daily oral administration of 10 mg/kg of the drugs, starting at the 24th hour of infection and continuing until the 40th day of infection. Therapeutic effect of each drug was assessed by mortality of the treated mice. All control mice which did not receive any drug died within the 20th day (in Exp. 1) and the 22nd day (in Exp. 2) of infection, while 25% (in Exp. 1) and 40% (in Exp. 2) of RFP-treated mice and 100% (in Exp. 1 and 2) of mice treated with any of the KRMs survived on the 40th day of infection. II. Experimental M. avium complex infection in mice Female beige mice (8-12 weeks old) were inoculated via tail vein with ca. 1 x 10(8) CFU of M. avium complex strain 31F093T, a mouse-virulent strain, suspended in 0.2 ml medium. Treatment of the mice with each drug (daily oral administration of 20 mg/kg) was started 24 hours after the inoculation, and was continued throughout 12 weeks of infection.(ABSTRACT TRUNCATED AT 250 WORDS)