Izvorni znanstveni članak

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

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

MATEJ ČRČEK ; University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000 Ljubljana, Slovenia
IZTOK GRABNAR orcid.org/0000-0003-3452-1499 ; University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000 Ljubljana, Slovenia
JURIJ AGUIAR ZDOVC ; University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000 Ljubljana, Slovenia
ŠTEFAN GROSEK orcid.org/0000-0001-5352-8173 ; University of Ljubljana, Faculty of Medicine, Department of Pediatrics, 1000 Ljubljana; University Medical Centre Ljubljana, Division of Obstetrics and Gynecology, Department of Perinatology, Neonatology Section, 1000 Ljubljana, Slovenia; University Medical Centre Ljubljana, Division of Paediatrics, Department of Paediatric Intensive Therapy, 1000 Ljubljana, Slovenia
MOJCA KEREC KOS orcid.org/0000-0003-4060-6739 ; University of Ljubljana, Faculty of Pharmacy, Department of Biopharmacy and Pharmacokinetics, 1000 Ljubljana, Slovenia

Sažetak

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.

Ključne riječi

gentamicin; population pharmacokinetics; NONMEM; priors; paediatrics; intensive care

Hrčak ID:

302290

URI

https://hrcak.srce.hr/302290

Datum izdavanja:

30.6.2023.

Posjeta: 295 *