rifampin and rifametane

The pharmacokinetics and tolerance of a single oral dose (150 mg) of a new 3-azinomethyl rifamycin (SPA-S-565, USAN rifametane) was compared with 150 mg of conventional rifampicin in six healthy volunteers. The mean maximum concentration (Cmax) of SPA-S-565 was 3.94 +/- 0.26 micrograms/ml, and resulted significantly higher as compared with the Cmax after rifampicin, which was 2.89 +/- 0.20 micrograms/ml. The mean maximum time (tmax) for SPA-S-565 was 2.1 +/- 0.3 h as compared with that of rifampicin, which was 1.6 +/- 0.3 h, the difference between these values not being statistically significant. The elimination half-life (t1/2) of SPA-S-565 was 17.5 +/- 2.6 h in contrast to the half-life of 2.8 +/- 0.26 h seen with rifampicin; the difference was found to be highly significant. The mean area under the serum concentration curve from 0 to the last detectable concentration (AUC0-t) and the mean area under the serum concentration-versus-time curve from 0 to infinity (AUC0-infinity) of SPA-S-565 were almost six times than those obtained with conventional rifampicin. The differences between the two compounds were highly significant. In all cases except one volunteer all the biochemical parameters remained within normal range following single oral dose administration of SPA-S-565. In one volunteer, although there was a slight rise in serum alkaline phosphatase above the normal range, the original value itself was at the very upper limit of the normal range (i.e., 80 IU/L). Although there was a significant increase in the levels of serum alkaline phosphatase, serum gamma-glutamyl transpeptidase (GGTP) and serum amylase levels, 24 h following the administration of SPA-S-565 these levels remained within the normal range.

Topics: Administration, Oral; Adult; Alkaline Phosphatase; Amylases; Analysis of Variance; Anti-Infective Agents; Antibiotics, Antitubercular; Area Under Curve; Cross-Over Studies; gamma-Glutamyltransferase; Half-Life; Humans; Male; Rifampin; Rifamycins

The in-vitro activity of a 3-azinomethyl-rifamycin (SPA-S-565) against Chlamydia trachomatis was compared to that of rifampicin and of erythromycin. The compound showed excellent activity for standard strains as well as isolates from patients with sexually transmitted diseases, being more active than the other drugs tested. SPA-S-565 also showed a low frequency of emergence of resistance. Passage of standard strains at sub-inhibitory concentrations caused an increase in MIC values of rifampicin while those for SPA-S-565 remained unchanged.

Topics: Anti-Bacterial Agents; Chlamydia trachomatis; Erythromycin; Humans; Microbial Sensitivity Tests; Rifampin; Rifamycins; Sexually Transmitted Diseases, Bacterial

The in vitro activities of two new long-acting rifamycins, FCE22807 a derivative of FCE22250, and CGP40/469A (SPA-S-565) were studied. When compared with rifampicin, the minimal inhibitory concentrations (MIC) against Mycobacterium tuberculosis of both were 4 times lower but neither was particularly active against rifampicin-resistant strains of M. tuberculosis nor against M. avium-intracellulare-scrofulaceum complex strains. A drug is likely to be particularly effective in widely spaced intermittent dosage if it has a long half-life and high bactericidal activity. When tested against M. tuberculosis in the logarithmic and in the stationary phase of growth, FCE22807 was amongst the most bactericidal of the rifamycins while CGP40/469A had little bactericidal activity.

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Drug Stability; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium tuberculosis; Rifampin; Rifamycins; Time Factors