Urine pH and Salicylate Therapy

To the Editor.—  The pronounced effect of urine pH on the renal clearance of salicylate is well known. Renal excretion is, however, only one of several pathways by which salicylate is eliminated from the body. The recently accomplished total characterization of the pharmacokinetics of salicylate elimination in man^1,2 has made it possible to carry out computer simulations of the time course of salicylate levels in the body during long-term drug administration under different conditions. These simulations predicted that relatively small changes in urine pH can cause a very marked change of salicylate concentrations in the plasma when relatively large doses of salicylate are used.We carried out a clinical study which confirmed this prediction. One gram of aspirin was given four times a day for seven days to 13 normal ambulatory adult volunteers, either with or without sufficient sodium bicarbonate ( about 4 gm/day) to increase urine pH somewhat (without