Optimizing Gentamicin Dosing in Pediatrics Using Monte Carlo Simulations


    loading  Checking for direct PDF access through Ovid

Abstract

Gentamicin is known to have concentration-dependent bactericidal activity, and its nephrotoxic effect is well described. We developed a population pharmacokinetic/pharmacodynamic model to optimize gentamicin dosing in pediatrics. Data were retrospectively collected for pediatric patients 1 month to 12 years of age, admitted to general pediatric wards or intensive care units and received gentamicin for suspected or proven Gram-negative infections at King Saud University Medical City, Riyadh, Saudi Arabia. A total of 306 gentamicin peak and trough concentrations sets from 107 patients were analyzed with mean (±standard deviation) patient age and weight of 4.5 ± 3.5 years and 16.7 ± 10.8 kg, respectively. Gentamicin pharmacokinetics were adequately described with a one compartment system (R2 = 0.82, bias = 1.75% and precision = 88% for population predictions and R2 = 0.94, bias = 5% and precision = 29% for individual predictions). The gentamicin pharmacokinetic parameters were as follows: volume of distribution = 8.9 L, total body clearance = 2.8 L/h for a 20-kg patient. Monte Carlo simulations showed that doses of 5–6 mg/kg/dose once daily are adequate only to treat infections with Gram-negative organisms having minimal inhibitory concentration less than 1 µg/mL. While, at minimal inhibitory concentration of 1 µg/mL, higher doses (7–8 mg/kg/dose once daily) are needed to maximize the efficacy of gentamicin. However, at minimal inhibitory concentration of 2 µg/mL, even a 10 mg/kg dose showed poor target attainment (52%). The finding of this study highlights the need to reevaluate the current breakpoints of gentamicin and also to assess the safety of higher doses of gentamicin in pediatrics.

    loading  Loading Related Articles