Pharmacokinetics of macrolides. Comparison of plasma, tissue and free concentrations with special reference to...

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 obtained with roxithromycin, followed by clarithromycin and azithromycin. The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin. 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 found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour.