Exploration of Drug-Drug Interactions and Initial Dosage Administration of Oxcarbazepine in Elderly Patients with Epilepsy
Hai-Bo Zhang, Su-Mei He, Jie Wang, Dong-Dong Wang, Zheng-Quan YuIntroduction:
This study aimed to investigate whether there were potential drug-drug interactions (DDI) of oxcarbazepine in elderly patients with epilepsy during clinical combination therapy and explore the optimal initial dosage regimen of oxcarbazepine for elderly patients with epilepsy.
Methods:
The effectiveness of oxcarbazepine was mainly determined by measuring the concentrations of its active metabolite, 10-hydroxycarbazepine (MHD). The study developed an MHD population pharmacokinetic (PPK) model for elderly patients with epilepsy using nonlinear mixed-effect modelling (NONMEM).
Results:
It was found that no combined medications significantly affected the pharmacokinetic processes of MHD. Further, we simulated and recommended the optimal initial dosages of oxcarbazepine suitable for elderly patients with epilepsy. Dosages of 20, 15, 10, and 5 mg/kg oxcarbazepine were recommended for elderly patients with epilepsy who weighed 40-46 kg, 46-55 kg, 55-76 kg, and 76-100 kg, respectively. At the same time, in accordance with the above administration plan, the probabilities of achieving the target concentrations of the oxcarbazepine active metabolite in elderly patients with epilepsy were 99.0-99.4%, 99.0-99.5%, 98.7-99.6%, and 98.7-99.7%, respectively.
Discussion:
The study explored potential DDIs and the initial dosage administration of oxcarbazepine in elderly patients with epilepsy for the first time. Combined medications did not cause DDI when used by elderly patients with epilepsy for treatment, demonstrating the high safety of oxcarbazepine in the treatment of elderly patients with epilepsy.
Conclusion:
This study recommended the initial dosages of oxcarbazepine for elderly patients with epilepsy. To achieve the same therapeutic concentration ranges, the dosages for elderly patients with epilepsy may need to be reduced.