Optimizing Gentamicin Dosing in Pediatrics Using Monte Carlo Simulations


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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 aged 1 month–12 years, admitted to general pediatric wards or ICUs 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 (± SD) 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/hr 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 MIC less than 1 mcg/ml. While, at MIC of 1 mcg/ml, higher doses (7-8 mg/kg/dose once daily) are needed to maximize the efficacy of gentamicin. However, at MIC of 2 mcg/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.

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