Pharmacokinetics of once daily intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients

Abstract

This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.