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

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Abstract
Summary 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 4mg and SMZ 20mg per kg, peak serum levels of approximately 2.0 µg/ml TMP and 28 µg/ml SMZ were achieved at 4hours 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±11.5ml/min, peritoneal dialysance was 5.1±0.5ml/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±5.7ml/min, peritoneal dialysance was 1.2±0.2ml/min, and renal clearance was negligible. The half lives of TMP and SMZ were 23.7±4.0h and 18.1±3.5h, 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 12h.