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Several studies have reported that trough levels may not be optimal for monitoring vancomycin therapy, because of overexposure and nephrotoxicity risks. Therefore, we developed a population pharmacokinetic model to optimize vancomycin dosing and monitoring in pediatrics.Data were retrospectively collected on 76 pediatric patients 1–12 years of age, admitted to general pediatric wards or intensive care units at King Saud University Medical City, Riyadh, Saudi Arabia. The predictability of 3 methods for calculating the area under the curve (AUC) at steady state was assessed for optimum vancomycin therapy monitoring. The 3 methods were simple linear regression, Bayesian approach and the 2-sample pharmacokinetic equation method. We also used Monet Carlo simulations to evaluate the dosing of vancomycin.A 1-compartment model adequately described the data. A strong correlation occurred between the observed and predicted AUC from 0 to 24 hours (AUC0–24h) calculated using the Bayesian approach with a trough sample only or pharmacokinetic equations based on 2 measured samples (R2 = 0.93 and 0.92, respectively). For the simple linear regression method with a trough sample only, the predicted AUC0–24h at steady state with vancomycin trough levels of 10, 15 and 20 µg/mL were 413, 548 and 714 µg·hour/mL, respectively. The target AUC0–24h above 400 was achieved in 46% and 95% of individuals with trough values of 7–11 and 11–15 µg/mL, respectively. Monte Carlo simulations showed that 60–80 mg/kg/d doses are needed to optimize vancomycin therapy.In conclusion, targeting vancomycin trough levels above 15 µg/mL in pediatrics would overshoot the target AUC0–24h above 400 and expose them to unnecessary adverse events.