Abstract
IntroductionThe 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.MethodsPopulation 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.
Highlights
The use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited
Gentamicin has been approved for use in the treatment of serious infections in all age groups, neonates to adults [1]
One main strategy that has been used and proven to Ghoneim et al Italian Journal of Pediatrics (2021) 47:167 ensure maximal efficacy while mitigating the risk of toxicities of aminoglycosides, including gentamicin, is once daily dosing. This strategy is based on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of gentamicin where a PK/PD index of free peak drug concentration above the minimum inhibitory concentration of the infecting organism should be the focus of dosing [2]
Summary
The use of once daily dosing of aminoglycosides in pediatrics is increasing but studies on dose optimization targeting the pediatric population are limited. One main strategy that has been used and proven to Ghoneim et al Italian Journal of Pediatrics (2021) 47:167 ensure maximal efficacy while mitigating the risk of toxicities of aminoglycosides, including gentamicin, is once daily dosing. This strategy is based on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of gentamicin where a PK/PD index of free peak drug concentration above the minimum inhibitory concentration of the infecting organism (fCmax/MIC) should be the focus of dosing [2]. The use of once daily dosing of aminoglycosides in pediatrics is increasing, especially in some disease states that require higher drug concentration due to increased drug clearance such as cystic fibrosis
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