R. Zachary Thompson, MPH, PharmD, BCPPS
Clinical Coordinator, PICU Pharmacist
Nationwide Children's Hospital At Ohio State University
Columbus, Ohio
Disclosure information not submitted.
Emma Wysocki, PharmD, RD
Pediatric Pharmacy Coordinator
Geisinger Medical Center
Danville, Pennsylvania
Disclosure information not submitted.
Title: Population pharmacokinetics of high-dose, extended-interval amikacin in critically ill children
Introduction: Amikacin pharmacokinetics may be altered in critically ill children due to their changes in volume of distribution and clearance. High-dose, extended interval dosing is proposed to ensure maximal pharmacodynamic targets of amikacin are achieved while keeping an appropriate safety profile. The primary objective of this study was to develop a population pharmacokinetic model for high-dose, extended-interval amikacin in critically ill children.
Methods: A retrospective chart review was performed on children between 1 and 18 years of age who received amikacin while admitted to the pediatric intensive care unit and had paired post-dose amikacin concentrations measured. Population-based pharmacokinetic modeling was performed using NONMEM 7.5 and PDx-Pop (ICON LLC) and simulations were performed to determine empiric doses to meet pharmacodynamic targets for amikacin.
Results: A total of 77 patients (52.4% male, median [IQR] age 11.4 [5.6, 14.9] years) met inclusion criteria with 164 concentrations included in the final analysis. The patients received a median of two doses of amikacin (median [IQR] dose 22.9 [19.8, 25.2] mg/kg of dosing weight) prior to serum concentration attainment. The median volume of distribution and total clearance were 0.37 L/kg (IQR 0.29-0.47) and 2.58 L/h (IQR 1.96 – 4.4), respectively. Pharmacokinetic modelling showed a one-compartment model with exponential error as the best fit, with weight and renal function as the covariates included in the model.
Conclusions: This is the first population pharmacokinetic analysis of high-dose, extended-interval amikacin in critically ill children. Clinical effectiveness studies are needed to determine the appropriate pharmacodynamic targets for amikacin when utilized in a high-dose, extended interval dosing scheme.