Pharmacokinetics of Intraperitoneal Cefepime in Automated Peritoneal Dialysis

Abstract

This study determined the pharmacokinetics of intraperitoneal (IP) cefepime in automated peritoneal dialysis (APD) patients. A prospective pharmacokinetic study was performed in 6 noninfected adult APD patients. All patients were administered a single IP dose of cefepime (15 mg/kg) over a 6-hour dwell. Patients then underwent a fixed APD regimen consisting of the first 6-hour dwell, followed by an 8-hour dialysate-free period and a subsequent series of 3 overnight APD exchanges. Blood and dialysate samples were collected at t = 0, 1, 2, 4, 6 (end of dwell), and 24 hours. Any urine produced during the study period was collected. Cefepime concentrations in serum, dialysate, and urine were determined by liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated assuming a mono-exponential model. One hour after IP administration, serum cefepime levels exceeded the minimum inhibitory concentration (8 microg/mL) for susceptible organisms. The mean serum and dialysate concentrations at 24 hours were 15.8 +/- 3.6 and 6.2 +/- 2.3 microg/mL respectively. Bioavailability was 84.3% +/- 6.2%, volume of distribution 0.34 +/- 0.07 L/kg, and serum half-life 13.8 +/- 3.2 hours. Total, peritoneal, and renal clearances were 16.5 +/- 4.4, 4.3 +/- 0.7, and 3.5 +/- 2.5 mL/minute, respectively. IP cefepime dosed at 15 mg/kg resulted in adequate serum concentrations in APD patients at 24 hours post dose. Pharmacokinetic predictions suggest that most APD and CAPD patients would achieve adequate serum cefepime concentrations if treated with standard doses of 1000 mg given IP once daily. Patients using APD regimens different from that used in this study, anuric patients, and those with significant residual renal function may require a more individualized approach.