External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents
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 pa...
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| Format: | Article |
| Language: | English |
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Sciendo
2023-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2023-0027 |
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| author | Črček Mateja Grabnar Iztok Zdovc Jurij Aguiar Grosek Štefan Kos Mojca Kerec |
| author_facet | Črček Mateja Grabnar Iztok Zdovc Jurij Aguiar Grosek Štefan Kos Mojca Kerec |
| author_sort | Črček Mateja |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3f9d5a681bcf41a6804ae05f278348d0 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2023-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-3f9d5a681bcf41a6804ae05f278348d02025-02-03T08:17:11ZengSciendoActa Pharmaceutica1846-95582023-06-0173217519410.2478/acph-2023-0027External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescentsČrček Mateja0Grabnar Iztok1Zdovc Jurij Aguiar2Grosek Štefan3Kos Mojca Kerec41University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000LjubljanaSlovenia1University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000LjubljanaSlovenia1University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000LjubljanaSlovenia2University of Ljubljana, Faculty of Medicine, Department of Pediatrics1000Ljubljana, Slovenia1University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000LjubljanaSloveniaThe 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.https://doi.org/10.2478/acph-2023-0027gentamicinpopulation pharmacokineticsnonmempriorspaediatricsintensive care |
| spellingShingle | Črček Mateja Grabnar Iztok Zdovc Jurij Aguiar Grosek Štefan Kos Mojca Kerec External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents Acta Pharmaceutica gentamicin population pharmacokinetics nonmem priors paediatrics intensive care |
| title | External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| title_full | External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| title_fullStr | External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| title_full_unstemmed | External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| title_short | External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| title_sort | external validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents |
| topic | gentamicin population pharmacokinetics nonmem priors paediatrics intensive care |
| url | https://doi.org/10.2478/acph-2023-0027 |
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