Objective: To evaluate the pharmacokinetics, safety, and tolerability of cefepime administered as an intravenous bolus and short infusion.
Methods: A single-dose, pharmacokinetic study was conducted on 16 healthy men. Fifty milliliters of a 40 mg/mL solution of cefepime was administered by continuous infusion in intervals of three, five, 10, or 15 minutes. Blood was sampled three minutes through 12 hours after the end of the infusion. Analysis of cefepime was performed by reverse-phase HPLC with ultraviolet detection. Cefepime plasma concentrations versus time were evaluated by noncompartmental methods. History and physical examinations were conducted within two weeks of the start of the study, 24 hours before dosing, and at the end of the study. Assessments for adverse events were made throughout the study.
Results: Maximum concentration (Cmax) increased with decreasing time of infusion and was similar to reference values of Cmax. Pharmacokinetic characteristics of cefepime were not affected by the time of infusion and were on average: mean residence time was 2.3 hours, half-life 1.9 hours, the AUC extrapolated to infinity 239 microg x h/mL, total body clearance 142 mL/min, and steady-state volume of distribution 19 L. No serious adverse events, local tolerance at injection site, or significant laboratory abnormalities were noted.
Conclusions: Cefepime 2 g was safely administered to healthy subjects as a rapid, single bolus, and its key pharmacokinetic parameters were consistent with those from longer infusions and other studies.