Observations on the Urinary Excretion of Sulfadiazine.

Although the kidney is the main excretory channel for the sulfonamide drugs' as well as the site of some of the most serious complications resulting from their use, the factors influencing their excretion have received less attention than they deserve. Marshall, Emerson, and Cutting (1) concluded from their studies on dogs that increasing the rate of urine flow apparently increased the renal clearance of sulfanilamide. Their findingwas subsequently supported by the work of Stewart, Rourke, and Allen (2) in human subjects. On the other hand, Alyea, Daniel, and Yates (3) and later Lucas and Mitchell (4) presented data which they interpreted as showing that sulfanilamide is excreted at a constant rate, irrespective of the urine volume. Bullowa and his coworkers (5) found, in patients, that sulfapyridine is excreted at an irregular rate which is independent of the rate of urine flow. Clearance rates of the various sulfonamide derivatives has indicated considerable degrees of tubular reabsorption (1, 6 to 12). The clinical impression is prevalent that excretion of sulfapyridine, sulfathiazole, and sulfadiazine can be hastened by "forcing fluids," and the procedure is usually recommended in patients who are exhibiting toxic effects from these drugs. There are no adequate data, however, to support this impression. In this paper are presented the results of attempts by various procedures to induce diuresis of drug and of urine in persons receiving sulfadiazine in ordinary therapeutic doses. An increase in the rate of excretion of drug may be of some advantage in patients who are exhibiting severe systemic reactions, such as drug rashes, fevers, or agranulocytosis. Water diuresis, on the other hand, would obviously be desirable in patients who manifest urinary tract irritation as a result of the precipitation of the drug. It was the purpose of this study to determine which of the procedures in common use most effectively produces these two results, either separately or simultaneously. MATERIALS AND METHODS