J. Wyngaarden
Feb 1, 1955
Citations
0
Influential Citations
29
Citations
Quality indicators
Journal
The Journal of clinical investigation
Abstract
Phenylbutazone is a potent analgesic compound widely used in the treatment of gout and other arthritic disorders. Both in gouty and non-gouty subjects the drug sharply reduces the serum urate level (1-8). The mechanism by which this is accomplished has recently received attention in several laboratories, but the results are discrepant. Some investigators report that the drug has a potent uricosuric effect (3, 4, 6, 7), others that the drug produces no important change in urate excretion (2, 5), and still others that it actually causes a diminution of urate output (8). The latter two results, if valid, could have several possible explanations, viz., the rate of urate synthesis has been reduced; uric acid has been disposed of by non-urinary pathways, or catabolized, in increased amounts; uric acid has been redistributed throughout a greater percentage of body water; or, uric acid has been greatly diluted in body fluids because of water retention and expansion of extracellular fluid volume. The present study was designed to evaluate these possible metabolic effects of phenylbutazone. Two normal subjects were'placed on constant low purine diets. Uric acid-N15 was infused during control periods and again during phenylbutazone administration, the miscible pool of uric acid and the rate of its turnover were determined, and the results obtained were correlated with changes in excretion values and serum concentrations of uric acid. Also, recoveries of unchanged isotopic uric acid in urine were determined in both periods, in order to evaluate extra-renal disposal or catabolism of urates. Finally, calculations of the volumes of distribution of uric acid were made; the changes observed were correlated with body weight and with hematocrit measurements in one subject. These studies have demonstrated that phenylbutazone is a uricosuric drug without specific effect on extra-renal factors of urate metabolism. METHODS