[The pharmacokinetics of josamycin]

Determination of the distribution coefficients in vitro demonstrates that josamycin (Wilprafen) is at least 15 times more lipophilic than erythromycin. On the other hand the distribution coefficients of penicillin G and of amoxicillin be in the hydrophilic range. The serum protein binding of josamycin is 15%, which is markedly less than with the other macrolides. These in vitro experiments show that small structural differences can alter the physicochemical and biological behaviour of an antibiotic, even when the molecules are closely related. A cross-over experiment with 12 volunteers and multiple application of 1 g of josamycin base or 1.175 g of erythromycin ethyl succinate showed that both macrolides are rapidly absorbed and reach their maximum within the first hour. In 21 patients the concentration of josamycin in lung tissue was 2 to 3 times that in the blood. The highest concentration of josamycin reached was 3.68 micrograms/g lung tissue (mean of 12 patients) and this was found for the group of patients from whom the tissue samples had been taken 2-3 h after the last administration of the drug. Lower mean concentrations of erythromycin were found in the serum and lung tissue of a similar group of 31 patients. The results indicate that the new macrolide antibiotic josamycin accumulates well in lung tissue and that the concentrations necessary for the treatment of infections (minimal inhibitory concentrations [MIC]) are rapidly reached also in the tissue.