Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

Abstract

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30-60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~ 0.2 L/kg in healthy adults with normal renal function. Protein binding is relatively low (20%), and elimination is mainly renal. About 85% of the dose is excreted unchanged in the urine, with an elimination half-life of 2-2.3 h. The pharmacokinetics of cefepime is altered under certain pathophysiological conditions, resulting in high inter-individual variability in cefepime volume of distribution and clearance, which poses challenges for population dosing approaches. Consequently, therapeutic drug monitoring of cefepime may be beneficial in certain patients including those who are critically ill, have life-threatening infections, or are infected with more resistant pathogens. Cefepime is generally safe and efficacious, with a goal exposure target of 70% time of the free drug concentration over the minimum inhibitory concentration for clinical efficacy. In recent years, reports of neurotoxicity have increased, specifically in patients with impaired renal function. This review summarizes the pharmacokinetics, pharmacodynamics, and toxicodynamics of cefepime contemporarily in the setting of increasing cefepime exposures. We explore the potential benefits of extended or continuous infusions and therapeutic drug monitoring in special populations.

Fig. 1

Variability in cefepime volume of distribution (V_d) in different pathological conditions. CrCL creatinine clearance, ESRD end-stage renal disease, GFR glomerular filtration rate

Fig. 2

Variability in cefepime clearance (CL) in different pathological conditions. CrCL creatinine clearance

Fig. 3

Hospital survival for those that reach their cefepime pharmacodynamic goal (blue triangles) and those who do not (red circles) as a function of the APACHE II score [106]