Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.

Autor:	Pérez-Blanco JS; Department of Pharmaceutical Sciences, University of Salamanca, Pharmacy Faculty, Campus Miguel de Unamuno, 37007 Salamanca, Spain.; Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Hospital Virgen de la Vega, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain., Sáez Fernández EM; Department of Pharmaceutical Sciences, University of Salamanca, Pharmacy Faculty, Campus Miguel de Unamuno, 37007 Salamanca, Spain.; Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Hospital Virgen de la Vega, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain.; Pharmacy Service, University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain., Calvo MV; Department of Pharmaceutical Sciences, University of Salamanca, Pharmacy Faculty, Campus Miguel de Unamuno, 37007 Salamanca, Spain.; Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Hospital Virgen de la Vega, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain.; Pharmacy Service, University Hospital of Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain., Lanao JM; Department of Pharmaceutical Sciences, University of Salamanca, Pharmacy Faculty, Campus Miguel de Unamuno, 37007 Salamanca, Spain.; Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Hospital Virgen de la Vega, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain., Martín-Suárez A; Department of Pharmaceutical Sciences, University of Salamanca, Pharmacy Faculty, Campus Miguel de Unamuno, 37007 Salamanca, Spain.; Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Hospital Virgen de la Vega, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2020 Aug 01; Vol. 75 (8), pp. 2222-2231.
DOI:	10.1093/jac/dkaa158
Abstrakt:	Objectives: To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage. Methods: A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation. An interactive model-based simulation tool was developed in R (Shiny and R Markdown). Cmax/MIC ratio, time above MIC and AUC/MIC were used for optimizing amikacin initial dose recommendation. Probabilities of reaching targets were calculated for the dosage proposed. Results: A one-compartment model with first-order linear elimination best described the 873 amikacin plasma concentrations available from 294 subjects (model development and external validation groups). Estimated amikacin population pharmacokinetic parameters were CL (L/h) = 0.525 + 4.78 × (CKD-EPI/98) × (0.77 × vancomycin) and V (L) = 26.3 × (albumin/2.9)-0.51 × [1 + 0.006 × (weight - 70)], where CKD-EPI is calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. AMKdose is a useful interactive model-based application for a priori optimization of amikacin dosage, using individual patient and microbiological information together with predefined pharmacokinetic/pharmacodynamic (PKPD) targets. Conclusions: Serum albumin, total bodyweight, estimated glomerular filtration rate (using the CKD-EPI equation) and co-medication with vancomycin showed a significant impact on amikacin pharmacokinetics. A powerful interactive initial dose-finding tool has been developed and is freely available online. AMKdose could be useful for guiding initial amikacin dose selection before any individual pharmacokinetic information is available. (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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