Kinetic studies on rifampicin. I. Serum concentration analysis in subjects treated with different oral doses over a period of two weeks.

Abstract

A study aimed at contributing to the elucidation of the decrease in serum rifampicin concentrations observed during repeated administration of the antibiotic was carried out in a group of 18 healthy subjects. Three dose levels were investigated: 900 mg once daily, 600 mg once daily and 300 mg 12-hourly, and the behaviour over a period of 14 days of the peak and 12-hour serum concentrations and of the biological half-life was evaluated. The study demonstrates that during treatment with repeated doses of rifampicin the kinetics of the antibiotic undergo definite changes. While the peak serum concentrations do not appear to be affected in a consistent way by the duration of treatment, the 12-hour serum concentrations show a definite decrease, which takes place mainly during the first 6 days of treatment; a further decrease between 6 and 14 days was seen but was found not to be significant. A definite decrease in biological half-life is also observed during the first 6 days of treatment; such a decrease is directly correlated with the dose given on each administration. As a consequence, the half-life values, which are correlated with the doses on the first day of treatment, are no longer different for the different doses on the sixth day. The hypothesis that the increase in rate of disappearance of rifampicin from blood, which takes place mainly during the first 6 days of treatment, is due to an increased rate of biliary excretion is discussed.