Pharmacokinetic and pharmacodynamic profiling of cefepime in plasma and peritoneal fluid of abdominal surgery patients

This study was conducted to characterise the pharmacokinetics and pharmacodynamics of cefepime in plasma and peritoneal fluid (PF). One gram of cefepime was administered to eight laparotomy patients and plasma and PF samples were collected at the end of 0.5 h infusion and every hour for 6 h. Drug concentrations were determined, analysed by population pharmacokinetic modelling and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. The maximum concentration in PF was two-thirds of the value in plasma; however, the concentrations were higher in PF than in plasma at 0.68 h post dose. The probabilities of attaining the pharmacodynamic target (65% of the time above the MIC) were 92-99% in plasma (90% fraction unbound) and 93-100% in PF against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae with a regimen of I g every 12 h. However, 1 g every 8 h or 2 a every 12 h was required for values of 94-95% in plasma and 95-96% in PF against Pseudomonas aeruginosa. These results demonstrate that the pharmacodynamic exposures in PF were almost identical to those estimated from plasma data and provided a pharmacokinetic/pharmacodynamic rationale for the dosing regimen for surgical intra-abdominal infections. (C) 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.