Pharmacokinetics of intravenous trimethoprim-sulfamethoxazole during hemodialysis.

The pharmacokinetics of intravenous trimethoprim-sulfamethoxazole (TMP-SMZ) were studied in patients receiving hemodialysis. 16 stable end-stage renal disease patients received a single ampul of TMP-SMZ (160 mg TMP, 800 mg SMZ) with 250 ml 5% dextrose and water over 45 min just prior to beginning hemodialysis. All patients were dialyzed for 4 h with a 1.0 m2 cuprophane hollow-fiber dialyzer at a blood flow of 200 ml/min. Mean arterial TMP concentration peaked at 1.93 micrograms/ml following infusion and fell to 1.03 micrograms/ml by the end of dialysis (p less than 0.001). Mean arterial SMZ concentration peaked at 41.8 micrograms/ml at the end of the infusion and fell to 16.4 micrograms/ml by the end of dialysis (p less than 0.005). The extraction ratio averaged 19% for TMP and 21% for SMZ. The elimination half-life during dialysis for TMP was 6.0 h and for SMZ was 3.1 h. Dialysis clearance averaged 38 ml/min for TMP and 42 ml/min for SMZ. 44% of the administered TMP and 57% of the administered SMZ were removed during dialysis. Therefore, 50% of the maintenance dose of TMP-SMZ should be supplemented after each dialysis session.