Sabrina De Winter1, Reinier van Hest2, Erwin Dreesen3,4, Pieter Annaert5,6, Joost Wauters7, Wouter Meersseman7, Nele Van den Eede8, Stefanie Desmet8, Sandra Verelst9, Peter Vanbrabant7, Willy Peetermans7, Isabel Spriet10,3. 1. Department of Pharmacy, Univesity Hospitals Leuven, Leuven, Belgium. sabrina.dewinter@uzleuven.be. 2. Department of Hospital Pharmacy and Clinical Pharmacology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. 3. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. 4. Department of Pharmacy, Uppsala University, Uppsala, Sweden. 5. Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. 6. BioNotus, Galileilaan 15, 2845, Niel, Belgium. 7. Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium. 8. Laboratory of Clinical Bacteriology and Mycology, University Hospitals Leuven, Leuven, Belgium. 9. Department of Emergency Medicine, University Hospitals Leuven, Leuven, Belgium. 10. Department of Pharmacy, Univesity Hospitals Leuven, Leuven, Belgium.
Abstract
BACKGROUND: There may be a difference between the determinants of amikacin exposure in emergency department (ED) versus intensive care (ICU) patients, and the peak amikacin concentration varies widely between patients. Moreover, when the first dose of antimicrobials is administered to septic patients admitted to the ED, fluid resuscitation and vasopressors have just been initiated. Nevertheless, population pharmacokinetic modelling data for amikacin in ED patients are unavailable. OBJECTIVE: The aim of this study was to quantify the interindividual variability (IIV) in the pharmacokinetics of amikacin in patients admitted to the ED and to identify the patient characteristics that explain this IIV. METHODS: Patients presenting at the ED with severe sepsis or septic shock were randomly assigned to receive amikacin 25 mg/kg or 15 mg/kg intravenously. Blood samples were collected at 1, 6 and 24 h after the onset of the first amikacin infusion. Data were analysed using nonlinear mixed-effects modelling. RESULTS: A two-compartment population pharmacokinetic model was developed based on 279 amikacin concentrations from 97 patients. The IIV in clearance (CL) and central distribution volume (V1) were 71% and 26%, respectively. Body mass index (BMI), serum total protein level, serum sodium level, and fluid balance 24 h after amikacin administration explained 30% of the IIV in V1, leaving 18% of the IIV unexplained. BMI and creatinine clearance according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation 24 h after amikacin administration explained 46% of the IIV in CL, and 39% remained unexplained. CONCLUSION: The IIV of amikacin pharmacokinetics in ED patients is large. Higher doses may be considered in patients with low serum sodium levels, low total protein levels, or a high fluid balance. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02365272.
BACKGROUND: There may be a difference between the determinants of amikacin exposure in emergency department (ED) versus intensive care (ICU) patients, and the peak amikacin concentration varies widely between patients. Moreover, when the first dose of antimicrobials is administered to septic patients admitted to the ED, fluid resuscitation and vasopressors have just been initiated. Nevertheless, population pharmacokinetic modelling data for amikacin in ED patients are unavailable. OBJECTIVE: The aim of this study was to quantify the interindividual variability (IIV) in the pharmacokinetics of amikacin in patients admitted to the ED and to identify the patient characteristics that explain this IIV. METHODS: Patients presenting at the ED with severe sepsis or septic shock were randomly assigned to receive amikacin 25 mg/kg or 15 mg/kg intravenously. Blood samples were collected at 1, 6 and 24 h after the onset of the first amikacin infusion. Data were analysed using nonlinear mixed-effects modelling. RESULTS: A two-compartment population pharmacokinetic model was developed based on 279 amikacin concentrations from 97 patients. The IIV in clearance (CL) and central distribution volume (V1) were 71% and 26%, respectively. Body mass index (BMI), serum total protein level, serum sodium level, and fluid balance 24 h after amikacin administration explained 30% of the IIV in V1, leaving 18% of the IIV unexplained. BMI and creatinine clearance according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation 24 h after amikacin administration explained 46% of the IIV in CL, and 39% remained unexplained. CONCLUSION: The IIV of amikacin pharmacokinetics in ED patients is large. Higher doses may be considered in patients with low serum sodium levels, low total protein levels, or a high fluid balance. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02365272.
Authors: A Marsot; S Hraiech; N Cassir; F Daviet; G Parzy; O Blin; L Papazian; R Guilhaumou Journal: Int J Antimicrob Agents Date: 2020-07-31 Impact factor: 5.283
Authors: Tingjie Guo; Alan Abdulla; Birgit C P Koch; Johan G C van Hasselt; Henrik Endeman; Jeroen A Schouten; Paul W G Elbers; Roger J M Brüggemann; Reinier M van Hest Journal: Clin Pharmacokinet Date: 2022-03-09 Impact factor: 5.577