INTRARENAL DISTRIBUTION OF PENICILLIN, CEPHALOTHIN, AMPICILLIN AND OXYTETRACYCLINE DURING VARIED STATES OF HYDRATION

¹ Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, and The National Center for Antibiotic Analysis, Food and Drug Administration, Department of Health, Education and Welfare, Washington, D. C.

After the constant infusion of an antibiotic, tissue concentrations of the drug measured within the cortex, medulla and papilla of the dog kidney show considerable variation depending upon the type of antibiotic and the state of hydration of the experimental animal. In the hydropenic state, a significant gradient of increasing concentration from cortex to papilla occurs with penicillin and cephalothin, whereas ampicillin and oxytetracycline concentrations do not differ between cortex, medulla and papilla. The increase in antibiotic concentration from cortex to papilla was 4-fold for penicillin and 3-fold for cephalothin. Hydration effectively dissipated these gradients. The increase in tissue gradients during hydropenia may be attributed in part to high antibiotic concentrations in medullary and papillary intratubular urine. However, it appears that the papillary tissue water concentration for some of the antibiotics may be significantly increased over concomitant serum levels. Papillary tissue water concentration of penicillin exhibited a 10-fold, cephalothin a 6-fold and oxytetracycline a 2-fold increase over simultaneously existing serum levels during hydropenia. This form of investigation provides a means for selecting antibiotics most effectively concentrated in the papillary and medullary tissues and yields information of potential therapeutic importance.