Pharmacokinetic modeling of vancomycin in children, pre-adolescent, and adolescent patients : development, assessment, and application

Abstract

The development and evaluation of a vancomycin population pharmacokinetic model in children, pre-adolescent, and adolescent patients was performed via non linear mixed effects modeling (NONMEM) in 2 phases. In phase I, a vancomycin population pharmacokinetic model was developed based on data from 200 children (aged 2-17 years) using a two-compartment model. Variables tested for inclusion in the model were serum creatinine (SCR), age (AGE), weight (WT), height (HT), sex (SEX), and body surface area (BSA). Variables were included at the p $In phase II, the performance of the derived model was evaluated in a naive tested population and then compared to the Schaad, et al. model via prediction error techniques (PE). The predictability of 159 measured concentrations was assessed in 68 new patients. In predicting all concentrations types, the mean prediction error (MPE) with a 95$-$1.42 ($-$3.38, 0.54), and 6.01 (4.46, 7.56) mg/L, respectively. When considering only peaks, a MPE with 95$-$0.94, 4.38), and 7.61 (5.13, 10.09) mg/L, respectively. Finally, MPE with 95$-$1.45 ($-$3.42, 0.52), and 3.84 (2.98, 4.70) mg/L, respectively. Maintenance dose (MD) tables were designed, based on the relationship of height and serum creatinine to clearance. In addition, a loading dose (LD) was also recommended, which was 5 mg/cm. It is recommended that the current study model be used for dosing the pediatric population while setting an initial target peak of 30 mg/L and a trough of 5-10 mg/L. This should frequently result in optimal serum vancomycin concentrations within the therapeutic window. Individualization of therapy should then be done, once the measured concentrations are available