Ordinary Differential Equation-Based Individualized Pharmacokinetic Simulation for Dose Optimization in an Infant with Global Developmental Delay and Drug-Resistant Epilepsy.

In children with epilepsy associated with global developmental delay (GDD), around 10-20% experience refractory epilepsy, often requiring multiple antiseizure drugs (ASDs). These ASDs have narrow therapeutic indices. Therapeutic drug monitoring is crucial for optimizing ASD therapy. In this case, an infant with GDD with TBC1D24 mutation and refractory seizures was admitted with uncontrolled seizures despite multiple ASDs. The patient's serum levels of valproic acid, carbamazepine, and phenytoin were subtherapeutic. Simulations were performed by solving the pharmacokinetic ordinary differential equations numerically to optimize the dose. The modifications were made for valproate (240 mg every 4 h) and carbamazepine (100 mg thrice a day) to achieve therapeutic concentrations. Serum drug levels, after dose adjustment, were within the therapeutic range. The patient experienced no further seizure episodes. This case highlights the importance of individualized pharmacokinetic simulation in optimizing drug doses instead of empirical dose adjustments.