Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin

Clin Biochem. 2010 Apr;43(6):589-98. doi: 10.1016/j.clinbiochem.2009.12.007. Epub 2009 Dec 28.

Abstract

Objectives: The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens.

Design and methods: 69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem. A multivariate analysis was performed to predict the beta-lactam PK using AMK PK parameters estimated from TDM and using pathophysiological variables.

Results: An optimal prediction model was identified for each PK parameter of each beta-lactam. The best predictor of each model was one of the AMK PK parameters estimated from TDM. Other variables included colloid solution, renal and hepatic biomarkers, age and body weight.

Conclusion: PK of the four beta-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the beta-lactam dosages in clinical practice.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amikacin / administration & dosage*
  • Amikacin / pharmacokinetics
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Calibration
  • Critical Illness / therapy*
  • Drug Dosage Calculations*
  • Drug Monitoring* / methods
  • Drug Synergism
  • Drug Therapy, Combination
  • Empirical Research
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Sepsis / blood
  • Sepsis / drug therapy*
  • Young Adult
  • beta-Lactams / administration & dosage*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Amikacin