Optimizing gentamicin dosing in different pediatric age groups using population pharmacokinetics and Monte Carlo
Ragia H Ghoneim1, Abrar K Thabit2, Manar O Lashkar2
1Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, 7027 Abdullah Al-Sulaiman Rd, Jeddah, 22254-2265, Saudi Arabia. rghoneim@kau.edu.sa.
Italian Journal of Pediatrics
|August 7, 2021
Summary
Optimizing gentamicin dosing in pediatrics using population pharmacokinetics is crucial. Once-daily dosing effectively achieves therapeutic targets while minimizing toxicity risks in children.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Pharmacokinetics
Background:
- Aminoglycoside dosing in pediatrics is shifting towards once-daily regimens.
- Limited studies exist on optimizing gentamicin doses specifically for pediatric populations.
- This research addresses the need for evidence-based dosing strategies in pediatric gentamicin therapy.
Purpose of the Study:
- To develop a population pharmacokinetic model for gentamicin in pediatric patients.
- To utilize the model for designing optimal once-daily gentamicin dosing regimens.
- To evaluate the probability of achieving therapeutic targets and maintaining safety profiles.
Main Methods:
- Retrospective chart review of pediatric patients' gentamicin plasma concentrations (peak/trough).
- Development of a two-compartment pharmacokinetic model with weight as a covariate.
- Monte Carlo simulations to assess target attainment (Cmax/MIC ≥ 10 mg/L) across various MICs (0.5-2 mg/L) and dosing regimens.
Main Results:
- A two-compartment model with additive residual error best described gentamicin pharmacokinetics.
- Weight was a significant covariate for clearance and volume of distribution.
- Simulations showed good probability of target attainment even at MIC of 2 mg/L, with specific doses for neonates (6-7 mg/kg/day) and older children (4-5 mg/kg/day).
- Trough concentrations remained below the toxicity limit of 1 mg/L.
Conclusions:
- Once-daily gentamicin dosing is a viable strategy in pediatrics.
- This dosing approach facilitates achievement of therapeutic targets.
- It effectively maintains trough gentamicin levels below toxicity thresholds.
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