Pharmacokinetic profile of a new 3-azinomethyl rifamycin (SPA-S-565) in volunteers as compared with conventional rifampicin.

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.