Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo simulation

Autor:	Manar O. Lashkar, Abrar K. Thabit, Ragia H. Ghoneim, Ahmed S. Ali
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Population Monte Carlo method Cmax Pediatrics RJ1-570 Pharmacokinetics medicine Humans Dosing education Child Gentamicin Monte Carlo simulation Retrospective Studies Volume of distribution education.field_of_study Dose-Response Relationship Drug business.industry Research Infant Newborn Infant Anti-Bacterial Agents Anesthesia Child Preschool Toxicity Linear Models Gentamicins business Monte Carlo Method medicine.drug
Zdroj:	Italian Journal of Pediatrics, Vol 47, Iss 1, Pp 1-8 (2021) Italian Journal of Pediatrics
ISSN:	1824-7288
Popis:	Introduction The use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited. This study aimed to derive a population pharmacokinetic model of gentamicin and apply it to design optimal dosing regimens in pediatrics. Methods Population pharmacokinetics of gentamicin in pediatrics was described from a retrospective chart review of plasma gentamicin concentration data (peak/ trough levels) of pediatric patients (1 month − 12 years), admitted to non-critically ill pediatrics. Monte Carlo simulations were performed on the resulting pharmacokinetic model to assess the probability of achieving a Cmax/MIC target of 10 mg/L over a range of gentamicin MICs of 0.5–2 mg/L and once daily gentamicin dosing regimens. Results: A two-compartment model with additive residual error best described the model with weight incorporated as a significant covariate for both clearance and volume of distribution. Monte Carlo simulations demonstrated a good probability of target attainment even at a MIC of 2 mg/L, where neonates required doses of 6-7 mg/kg/day and older pediatrics required lower daily doses of 4–5 mg/kg/day while maintaining trough gentamicin concentration below the toxicity limit of 1 mg/L. Conclusion: Once daily dosing is a reasonable option in pediatrics that allows target attainment while maintaining trough gentamicin level below the limits of toxicity.
Databáze:	OpenAIRE
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