Uptake of antibiotics by human erythrocytes.

Human erythrocytes have been used as a model system for the study of uptake and release of antibiotics. Penicillin G, dicloxacillin, tetracycline, and minocycline were all taken up by the cells, but each showed a characteristic ratio of distribution between the extracellular and intracellular compartments. Comparison of the penicillin analogues indicated that dicloxacillin, the more lipid-soluble compound, reached higher intracellular concentrations than did penicillin G. Use of human plasma as the incubation medium markedly decreased antibiotic uptake and enhanced antibiotic egress from preloaded cells. These effects were related to the binding of drugs to serum proteins. In vivo studies in which penicillin G was injected intravenously by bolus and was then given by constant infusion showed that intraerythrocytic concentrations of drug after 2 hr approached or exceeded those in plasma. These results can be explained, in part, by the fact that the slower rate of efflux of penicillin G from the cells than of clearance from plasma serves to maintain the high initial levels of drug for a longer period.