Cefazolin and cephalexin kinetics in continuous ambulatory peritoneal dialysis

We studied single-dose cefazolin (CFZ) and cephalexin (CPX) kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients to establish therapeutic guidelines for two cephalosporins commonly used to treat peritonitis in these patients. CFZ, 10 mg/kg, was given intravenously and intraperitoneally, while CPX, 500 mg, was given orally. CFZ led to serum concentrations of 25 microgram/ml at 24 hr, with a half-life (t 1/2) of 33 hr. CAPD accounted for only 20% of total body clearance. When CFZ was given intraperitoneally, 74% of the dose was absorbed and similar serum concentrations had much the same t 1/2. CPX, on the other hand, had a serum t 1/2 of 8.6 hr and resulted in much lower peritoneal concentrations than CFZ. The kinetic principal of superposition provided a model for the prediction of plasma concentrations after repeated intraperitoneal doses of CFZ. The model predicts that a 10-mg/kg intraperitoneal loading dose, followed by 5-mg/kg doses in each exchange the first day and 2.5-mg/kg doses thereafter, will lead to steady-state plasma concentrations of 50 to 65 microgram/ml. The data suggest that CFZ needs be given only intraperitoneally at doses lower than those in current use. CPX probably adds little to the treatment of peritonitis.