Pharmacokinetics of cefepime: a review.
The pharmacokinetic profile of cefepime following single and repeated i.v. or im administration was evaluated in healthy volunteers (n = 130), volunteers with renal failure (n = 42), elderly volunteers (n = 24), and in infected patients (n = 10). Following a 30 min iv infusion of between 250 and 2000 mg, the maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) increased in proportion to the dose, indicative of linear kinetics. The Cmax ranged between 16.3 and 133 mg/L, with corresponding AUC values ranging between 34 and 263 mg.h/L. The elimination half-life (T1/2) was approximately 2 h and was dose-independent. Total clearance (Cltot) for all doses ranged between 122 and 136 mL/min. Renal clearance (Clren) varied between 96 and 116 mL/min, suggesting that cefepime is eliminated mainly by glomerular filtration. No probenecid studies have been performed. Urinary excretion was comparable at all dose levels, with the parent compound accounting for > 80% of the recovered dose (i.v. or im). Following single im doses of between 250 and 2000 mg, absorption was rapid and the Tmax was attained in 1-1.6 h. Values for Cmax and AUC increased in a dose-proportional manner. The T1/2 was approximately 2 h and independent of dose. The bioavailability following im administration of 2000 mg was 100%. No accumulation following multiple i.v. or im dosing over 10 days was observed. Binding to plasma proteins was 16%. The volume of distribution at steady-state (Vdss) varied between 18 and 22 L and was dose-independent. The pharmacokinetic profiles of cefepime following single and repeated doses suggest that twice-daily administration by either the i.v. or im route is adequate to treat most infections caused by susceptible bacteria.