Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther

Ten adult patients on continuous ambulatory peritoneal dialysis (CAPO) received one dose of trimethoprim320 mg (TMP) and sulfamethoxazole 1600 mg (SMX) orally (p.o.), intravenously (i.v.), and intraperitoneally (i.p.) on three separate occasions to characterize the pharmacokinetics of both drugs. Concentrations of both TMP and SMX were measured in serum and dialysate by HPLC to 48 h. Half-Iife, total body clearance (TBC), and peritoneal clearance (PCI) were determined. The mean half-Iife of TMP was 28 h, while for SMX it was 12.5 h. Relative to the i.v. dose, the bioavailability following oral administration for TMP was 98 % and 87 % for SMX. Intraperitoneal bioavailability was 73 % for TMP and 65 % for SMX after a 4-h dwell. After 24 h, regardless of the route of administration, less than 3 % of TMP and less than 6 % of SMX appeared in dialysate. We conclude that peritoneal losses contribute insigni ficantly to TMPISMX elimination during CAPO. KEY WORDS: Trimethoprim; sulfamethoxazole; phar-macokinetics; bioavailability; continuous ambulatory peritoneal dialysis (CAPD). C ontinuous ambulatory peritoneal dialysis (CAPD) has become an established and important alter native treatment for end-stage renal disease. In 1985, almost 40 % of new dialysis patients in Canada were started on CAPD (1). However, dependent on age, only 40 to 60% remain on CAPD for three years (1,2). Peritonitis is responsible for 44 % of treatment failures and two-thirds of patients are likely to suffer at least one episode of peritonitis during their first year of CAPD treatment (3). Treatment of peritonitis is responsible for a major proportion of CAPD program costs (4). Given the clinical and economic importance ofperi tonitis in CAPD patients, and the failure of other methods (5-15) of reducing the peritonitis rate, w