Pharmacokinetics of intermittent intraperitoneal cefazolin in continuous ambulatory peritoneal dialysis patients

Objective:To investigate the pharmacokinetic parameters of intermittent int raperitoneal(IP) cefazolin, and recommend a cefazolin dosing regimen in con tinuous ambulatory peritoneal dialysis (CAPD) patients. Design: Prospective nonrandomized open study. Setting: CAPD outpatient clinic in Albany, New York. Patients: Seven volunteer CAPD patients without peritonitis. Three of the p atients were nonanuric while 4 were anuric. Interventions: Cefazolin (15 mg/kg total body weight) was given to each pat ient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1,2, 3, 6 (end of the first antibiotic-containi ng dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. Results:The means SD amount of cefazolin dose absorbed from the dialysate a fter the B-hour dwell was 69.7% +/- 8.0% of the administered dose. The cefa zolin absorption rate constant from dialysate to serum was 0.21 +/- 0.1 /hr (absorption half-life 3.5 +/- 0.8 hr). The mean serum concentrations reach ed at 24 and 48 hours were 52.4 +/- 3.7 mg/L and 30.3 +/- 5.9 mg/L, respect ively. The mean dialysate cefazolin concentrations reached at 24 and 48 hou rs were 15.1 +/- 3.4 mg/L and 7.9 +/- 1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02 +/- 0.01 /hr (elimination half-li fe 31.5 +/- 8.8 hr). The total cefazolin body clearance was 3.4 +/- 0.6 mL/ min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6 +/- 0.4 mL/min. The peritoneal clearance of cefazolin was 1.0 +/- 0.3 m L/min. The systemic volume of distribution of cefazolin was 0.2 +/- 0.05 L/ kg. No statistical difference was detected in pharmacokinetic parameters be tween anuric and nonanuric patients, although this may be due to the small number of patients in each group. Conclusion: A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration level s greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution i s warranted in extrapolation of dosing recommendations to patients who main tain a significant degree of residual renal function.