Trimethoprim-Sulfamethoxazole: Pharmacodynamic Effects of Urinary pH and Impaired Renal Function

Trimethoprim-sulfamethoxazole therapy was studied in persons with normal and impaired renal function, who were given a single oral dose of the combined drug. Oral acid loading increased the quantitative recovery of trimethoprim in urine but had no effect on urinary recovery of nonacetylated sulfamethoxazole. In contrast, alkali loading increased the urinary recovery of nonacetylated sulfamethoxazole and decreased the recovery of trimethoprim. The ratio of urinary concentration of sulfamethoxazole to trimethoprim was dependent on urine pH. A single dose of the combined drugs in uremic patients was associated with a prolonged half-life in blood and reduced quantitative recovery in urine for both drugs. The serum protein binding of sulfamethoxazole but not trimethoprim was reduced in uremic patients. Concentrations of both drugs in the urine of uremic patients seemed adequate for most susceptible urinary tract organisms. Trimethoprim-sulfamethoxazole may be useful for treating urinary infections in uremic patients.