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<p>The aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age groups, from preterm newborns to adolescents. We first selected published population pharmacokinetic models of gentamicin developed in the paediatric population with a wide age range. The parameters of the literature models were then re-estimated using the PRIOR subroutine in NONMEM<sup>®</sup>. The predictive ability of the literature and the tweaked models was evaluated. Retrospectively collected data from a routine clinical practice (512 concentrations from 308 patients) were used for validation. The models with covariates characterising developmental changes in clearance and volume of distribution had better predictive performance, which improved further after re-estimation. The tweaked model by Wang 2019 performed best, with suitable accuracy and precision across the complete paediatric population. For patients treated in the intensive care unit, a lower proportion of patients would be expected to reach the target trough concentration at standard dosing. The selected model could be used for model-informed precision dosing in clinical settings where the entire paediatric population is treated. However, for use in clinical practice, the next step should include additional analysis of the impact of intensive care treatment on gentamicin pharmacokinetics, followed by prospective validation.</p>
</abstract>

The aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age groups, from preterm newborns to adolescents. We first selected published population pharmacokinetic models of gentamicin developed in the paediatric population with a wide age range. The parameters of the literature models were then re-estimated using the PRIOR subroutine in NONMEM®. The predictive ability of the literature and the tweaked models was evaluated. Retrospectively collected data from a routine clinical practice (512 concentrations from 308 patients) were used for validation. The models with covariates characterising developmental changes in clearance and volume of distribution had better predictive performance, which improved further after re-estimation. The tweaked model by Wang 2019 performed best, with suitable accuracy and precision across the complete paediatric population. For patients treated in the intensive care unit, a lower proportion of patients would be expected to reach the target trough concentration at standard dosing. The selected model could be used for model-informed precision dosing in clinical settings where the entire paediatric population is treated. However, for use in clinical practice, the next step should include additional analysis of the impact of intensive care treatment on gentamicin pharmacokinetics, followed by prospective validation.

External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents

University of Ljubljana, Faculty of Pharmacy

Department of Biopharmacy and Pharmacokinetics

University of Ljubljana, Faculty of Medicine

University Medical Centre Ljubljana Division of Obstetrics and Gynecology

Department of Perinatology Neonatology Section

University Medical Centre Ljubljana Division of Paediatrics

Department of Paediatric Intensive Therapy

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age...

External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents

Publié en ligne: 12 juin 2023

Pages: 175 - 194

Accepté: 04 mai 2023

DOI: https://doi.org/10.2478/acph-2023-0027

Mots clés
gentamicin, population pharmacokinetics, NONMEM, priors, paediatrics, intensive care

© 2023 Mateja Črček et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents

Publié en ligne: 12 juin 2023

Pages: 175 - 194

Accepté: 04 mai 2023

DOI: https://doi.org/10.2478/acph-2023-0027

Mots clésgentamicin, population pharmacokinetics, NONMEM, priors, paediatrics, intensive care

© 2023 Mateja Črček et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Mots clés
gentamicin, population pharmacokinetics, NONMEM, priors, paediatrics, intensive care