Evaluation of slow infusions of co-trimoxazole by using predictive pharmacokinetics

Digital computer simulations of plasma concentration-time profiles of single intravenous infusions of trimethoprim (160 mg)/sulfamethoxazole (800 mg) based on data from other workers showed that increasing the infusion period from the hitherto generally recommended 1 to 1.5 h to 6 h did not significantly affect the interval (approximately 10 h and 8.5 h, respectively) during which trimethoprim and sulfamethoxazole plasma concentrations were maintained above their minimum effective plasma concentrations (selected as 0.6 microgram/ml and 25 microgram/ml, respectively). For the 6-h infusion, the simulated peak plasma concentration of trimethoprim was only approximately 27% less than for the 1-h infusion, and that for sulfamethoxazole was approximately 30% less. The validity of these predictions was confirmed by plasma concentration measurements of trimethoprim and sulfamethoxazole in six patients undergoing gynecological surgery, who received co-trimoxazole (160 mg of trimethoprim, 800 mg of sulfamethoxazole) postoperatively by constant-rate intravenous infusion over a 4-h period. It is concluded that infusions of the dose of intravenous co-trimoxazole over periods from 1 to at least 6 h are therapeutically equivalent.