Kinetics of a sulfadiazine-trimethoprim combination

The pharmacokinetics of a combination of sulfadiazine and trimethoprim has been studied in 16 patients with varying degrees of reduced renal function. In normal renal function, the serum half-life (t1/2) of active sulfadiazine, total sulfadiazine, and trimethoprim were quite close: 7.7, 9.6, and 12.1 hr, respectively. There was a gradual increase in serum t1/2 with reduction in renal function for both active and total sulfadiazine and for trimethoprim. With accurate determinations of endogenous renal clearance, t1/2 estimates may be made from regression curves presented. The relative distribution in the body was unrelated to renal function. It was similar for the two fractions of sulfonamide and higher for trimethoprim. The means were 0.371, 0.176, and 1.104 L/kg, respectively, for active and total sulfadiazine, and trimethoprim.