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.
D000328:Adult; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014295:Trimethoprim / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
D000892:Anti-Infective Agents, Urinary; D004338:Drug Combinations; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013420:Sulfamethoxazole