Physiologically based pharmacokinetic model for oxcarbazepine active metabolite to predict pharmacokinetics in paediatric patients with renal impairment and adjust dosages

Aims Oxcarbazepine (OXC) has been approved as monotherapy or adjunctive therapy for paediatric partial seizures. There are few reports on the pharmacokinetics (PK) of OXC in paediatric patients with renal impairment (RI), especially dosage studies of RI, which are rarely conducted on paediatric patients. This study aimed to predict the PK of OXC in children with RI and to provide recommendations for dose adjustment in this population. Methods Physiologically based pharmacokinetic (PBPK) models of the active metabolites of OXC were developed and verified, and their disposition was simulated in populations with or without RI. Results A fold error value of less than 2 was observed based on the simulated results from PBPK models for single‐ and multi‐dose administration. Based on the predictions for paediatric patients with moderate, severe, and end‐stage RI, the dose should be adjusted to 50, 40 and 25% of the normal dose, respectively, in children aged 2–5 years; and 50, 30 and 20%, respectively, in children aged 6–17 years. Conclusions The developed PBPK model is a valuable tool for predicting the OXC dosage in paediatric patients with RI.