Phenacetin: renal tubular transport and intrarenal distribution in the dog.

In a total of 22 studies in the anesthetized dog, the renal clearnace of phenacetin was measured over a range of plasma concentrations and at different urinary pH and rates of urine flow. Phenacetin is reabsorbed by passive diffusion. The urine/plasma ratio is essentially unity under all conditions. As measured by ultraviolet-spectrophotometric and colorometric methods and by high-pressure liquid chromatography, a labile metabolite appears in urine and renal papilla which upon hydrolysis gives rise to falsely high values for phenacetin. Renal cortical and papillary concentrations were determined in six dogs during hydropenia or diuresis. All tissue/plasma concentration ratios for phenacetin were essentially unity. The results indicate that the papillary localization of the earliest lesions of analgesic nephropathy cannot be attributed to high phenacetin concentrations within the papilla. This is in contrast to acetaminophen, the major metabolite of phenacetin.