PHARMACOKINETICS OF MACROLIDES - COMPARISON OF PLASMA, TISSUE AND FREE CONCENTRATIONS WITH SPECIAL REFERENCE TO ROXITHROMYCIN

When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtain ed with roxithromycin, followed by clarithromycin and azithromycin. Th e corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the sa me order of magnitude and the highest values are again those of roxith romycin, With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen. Intra-group subject variations (adults, children , the elderly etc.) were smaller than anticipated. Roxithromycin is fo und in-high and similar concentrations both in plasma and tissue, demo nstrating a balanced pharmacokinetic behaviour.