2. Academic Validation
  3. Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

Clinical Pharmacokinetics and Pharmacodynamics of Cefepime

  • Clin Pharmacokinet. 2022 Jul;61(7):929-953. doi: 10.1007/s40262-022-01137-y.
Gwendolyn M Pais 1 2,  Jack Chang 1 2,  Erin F Barreto 3,  Gideon Stitt 4,  Kevin J Downes 4 5 6,  Mohammad H Alshaer 7 8,  Emily Lesnicki 9,  Vaidehi Panchal 10,  Maria Bruzzone 11,  Argyle V Bumanglag 12 13,  Sara N Burke 12 13,  Marc H Scheetz 14 15
Affiliations

Affiliations

  • 1 Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, 555 31st St., Downers Grove, IL, 60515, USA.
  • 2 Chicago College of Pharmacy Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL, USA.
  • 3 Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.
  • 4 Center for Clinical Pharmacology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 5 Division of Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 6 Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • 7 Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
  • 8 Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
  • 9 College of Graduate Studies, Midwestern University, Downers Grove, IL, USA.
  • 10 Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
  • 11 Division of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA.
  • 12 Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA.
  • 13 Cognitive Aging and Memory Center, College of Medicine, University of Florida, Gainesville, FL, USA.
  • 14 Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, 555 31st St., Downers Grove, IL, 60515, USA. [email protected].
  • 15 Chicago College of Pharmacy Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL, USA. [email protected].
PMID: 35764774 DOI: 10.1007/s40262-022-01137-y
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.

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