Kinetics of the uptake of antimicrobial agents by human polymorphonuclear leucocytes.

The in-vitro rate constants of the cellular uptake and elimination of the antimicrobial agents josamycin (Wilprafen), erythromycin and tetracycline were measured in normal human polymorphonuclear leucocytes (PMNs) using the velocity gradient centrifugation technique with radiolabelled drugs at extracellular concentrations corresponding to therapeutically effective serum levels. The rate of antibiotic uptake increased stepwise in the order tetracycline less than erythromycin less than josamycin. The half-lives of the uptake came to 0.8 min for josamycin, 4.7 min for erythromycin, and 14.8 min for tetracycline. The extraordinarily rapid uptake of josamycin by PMNs corresponds to the high lipophility of the drug. The accumulation of the three tested antibiotics in PMNs occurred much faster than their elimination from the cells, suggesting directional transport of the molecules through the leucocyte membrane and/or rate limiting dissociation from intracellular binding sites. Significant differences between the drugs tested were observed in the temperature dependence of their rates of uptake. The apparent activation energies of cellular uptake amounted to 114.2 kJ mol-1 (josamycin), 68.6 kJ mol-1 (erythromycin) and 52.2 kJ mol-1 (tetracycline). There is experimental support for a contribution of the nucleoside carrier system to the membrane transport of josamycin.