Rodrigues C, et al. – The researchers established a parent–metabolite population pharmacokinetic model in children, in order to determine the consistency between the recommended pediatric doses and the reference range for trough concentration (C_trough) of monohydroxy derivative metabolite (MHD) (3–35 mg/L). This population pharmacokinetic model of oxcarbazepine supported the current dose recommendations, except for 10kg children with concomitant enzyme–inducing antiepileptic drugs (EIAEDs) and 50kg children without EIAEDs.

Methods

• In this study, after a single dose of oxcarbazepine, a total of 279 plasma samples were collected from 31 epileptic children (2–12y) .
• With Monolix 4.3.2, concentration–time data were evaluated.
• The probability to obtain C_trough between 3–35 mg/L was determined by Monte Carlo simulations for doses ranging from 10 to 90 mg/kg/day.

Results

• In investigations, a parent–metabolite model with two compartments for oxcarbazepine and one compartment for MHD best described the data.
• Typical values for oxcarbazepine clearance, central and peripheral distribution volume and distribution clearance were 140 L/h/70kg, 337 L/70kg, 60.7 L, and 62.5 L/h respectively.
• Findings displayed that typical values for MHD clearance and distribution volume were 4.11 L/h/70kg and 54.8 L/70kg respectively.
• Clearances and distribution volumes of oxcarbazepine and MHD were related to body weight via empirical allometric models.
• Enzyme–inducing antiepileptic drugs (EIAEDs) increased MHD clearance by 29.3%.
• 50 kg children without EIAEDs might need 20–30 mg/kg/day instead of the recommended target maintenance dose (30–45 mg/kg/day) to obtain C_trough within the reference range.
• By contrast, 10kg children with EIAEDs would need 90 mg/kg/day instead of the maximum recommended dose of 60 mg/kg/day.