Population pharmacokinetics of four β-lactams in critically ill septic patients comedicated with amikacin

Objectives: The study aimed to characterize the pharmacokinetics (PK) of four beta-lactams (piperacillin, ceftazidime, cefepime, and meropenem) in patients comedicated with amikacin (AMK), and to confirm the predictive performance of AMK data, obtained from therapeutic drug monitoring (TDM), on these PK, using a population modeling approach. Design and methods: Serum samples were collected in 88 critically ill septic patients. For each beta-lactam, the covariate model was optimized using renal function. Furthermore, predictive performance of AMK concentrations and PK parameters was assessed on beta-lactam PK. Results: A two-compartment model with first-order elimination best fitted the beta-lactam data. Results supported the superiority of AMK concentrations, over renal function and AMK PK parameters, to assess the beta-lactam PK. Conclusion: The study confirmed the significant link between the exposure to AMK and to beta-lactams, and presented population models able to guide beta-lactam dosage adjustments using renal biomarkers or TDM-related aminoglycoside data. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.