The Effect of Peritonitis on the Transperitoneal Transport of Cefuroxime in Patients on CAPD Treatment

Abstract

The pharmacokinetics and transperitoneal transport of cefuroxime were investigated in CAPD patients without peritonitis (n = 6), receiving 500 mg of the drug intravenously (i.v.) and intraperitoneally (i.p.) on separate occasions. CAPD patients with peritonitis were also investigated after i.p. administration of an initial dose of 500 mg cefuroxime followed by repeated doses of 250 mg. Routine hospital CAPD procedures and dwell-time schedules were followed during the study, and frequent blood and dialysate samples were collected. Cefuroxime was analysed by HPLC methods, and pharmacokinetic parameters were calculated. In the patients without peritonitis, the following pharmacokinetic parameters after i.v. and i.p. administration did not differ significantly (mean +/- SD): elimination half-life, 15.1 +/- 1.9 h; apparent volume of distribution 27.9 +/- 2.91; and total clearance, 21.5 +/- 1.2 ml/min. In contrast, the transperitoneal transport of cefuroxime differed significantly in the three studies. After i.v. administration the apparent transperitoneal clearance was low and time dependent, ranging from 4.2 +/- 1.2 to 1.4 +/- 0.4 ml/min. After i.p. administration the apparent transperitoneal clearance increased to 10.9 +/- 2.4 ml/min, whereas in the peritonitis patients a further increase to 21.5 +/- 3.5 ml/min was observed. In all patients we found cefuroxime concentrations in serum and dialysate, greatly exceeding MIC values of most pathogens involved in CAPD peritonitis and other systemic bacterial infections.