Pharmacokinetics of sulfamethoxazole--trimethoprim combination during chronic peritoneal dialysis: effect of peritonitis.

ABSTRACT

The pharmacokinetics of the fixed combination trimethoprim sulfamethoxazole (TMP--SMZ), including peritoneal transfer, has been studied in patients with end-stage renal disease treated by peritoneal dialysis, intermittent in 18 cases and continuous ambulatory dialysis in 6 cases. After a single oral dose of TMP 4 mg and SMZ 20 mg per kg, peak serum levels of approximately 2.0 micrograms/ml TMP and 28 micrograms/ml SMZ were achieved at 4 hours for TMP, and at 6 hours for SMZ. The protein binding of TMP was 34.7 +/- 1.1% and its distribution volume was 2.2 +/- 0.51/kg. Total plasma clearance of TMP was 66.2 +/- 11.5 ml/min, peritoneal dialysance was 5.1 +/- 0.5 ml/min, and renal clearance was negligible. The protein binding of SMZ was 48.0 +/- 1.4% and the distribution volume was 0.55 +/- 0.071/kg. Total plasma clearance of SMZ was 26.2 +/- 5.7 ml/min, peritoneal dialysance was 1.2 +/- 0.2 ml/min, and renal clearance was negligible. The half lives of TMP and SMZ were 23.7 +/- 4.0 h and 18.1 +/- 3.5 h, respectively. The peritoneal dialysance both of TMP and SMZ after oral administration was very low. In contrast the absorption after intra-peritoneal administration is high. Peritoneal absorption was increased during peritonitis. In patients with peritonitis, the intra-peritoneal administration of TMP-SMZ resulted in an immediate high local concentration, and a serum concentration of both drugs in the therapeutic range within 6 to 12 h.