An approach to the interpretation of drug concentrations in the kidney

Limited data are available defining the renal parenchymal concentrations and intrarenal distribution characteristics of drugs used in the therapy of renal disease, and interpretation of these data presents major difficulties. The authors have approached this problem by attempting to define the volume of renal papilla and medulla occupied by intraluminal contents in the hydropenic and hydrated in vivo kidney, based upon comparison of volume of distribution of different substances whose classic mechanisms of renal excretion are already well defined. To identify such anatomic volume estimates the authors investigated the intrarenal distribution patterns of 14C inulin and 3H para-aminohippuric acid (PAH) in the dog. The authors compared these results with their earlier studies delineating the intrarenal distribution characteristics of penicillin G and ampicillin. These studies permit definition of a theoretic volume of renal papilla and medulla required to contain the measured levels of inulin, PAH, penicillin G or ampicillin if the latter two drugs were hypothetically distributed within the intraluminal space of the medulla-papilla at a concentration equal to that measured in the urine. Ampicillin required the smallest theoretic volume of distribution in the hydropenic papilla during production of acid urine (1.4% ± SE 0.08), followed by PAH (2.47% ± 0.26), inulin (2.9% ± 0.34) and penicillin (4.2% ± 0.7). Therefore, in these studies the anatomic confines of the intraluminal space of the hydropenic papilla approximate 1.4% to 2.9% of the total tissue volume. Increase in urine flow rate progressively expands the papillary-medulla intraluminal volume. The volume distribution of a compound greater that that of the anatomic intraluminal space must therefore represent the fraction of medullary-papillary drug concentration distributed in the interstitial and intracellular compartments of the medulla-papilla.