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.
D000328:Adult; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014295:Trimethoprim / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism
D004338:Drug Combinations; D014295:Trimethoprim; D013420:Sulfamethoxazole