Precision dosing of perampanel in pediatric patients receiving oxcarbazepine combination therapy: physiologically based pharmacokinetic modeling and simulation.
Si-Ting Liu, Cheng-Jie Ke, Jing Su, Yu-Die Qian, Wan-Hong Wu, Xi Lin, Wei-Wei Lin
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引用次数: 0
Abstract
Background: The combination of oxcarbazepine (OXC) with perampanel (PER) considerably reduces the blood concentration of PER in children, decreasing the antiepileptic effect of PER. This study aimed to predict PER exposure and provide recommendations for dose adjustment in pediatric patients.
Research design and methods: Physiologically based pharmacokinetic (PBPK) models of PER and OXC for adults and pediatrics were developed and verified, followed by drug - drug interaction (DDI) modeling and validation of the models against available pharmacokinetic data.
Results: The simulated results of the PBPK models exhibited a fold-error value between 0.5 and 2, indicating good predictive abilities; the DDI model results supported the observational results. Based on the prediction results, the recommended dosages of PER for 4-10- and 10-14-year-old children are 2-6 and 4-8 mg q.n., respectively. Additionally, the recommended doses of PER in PER with OXC combination therapy for children aged 4-10 and 10-14 years are 6-12 and 10-12 mg q.n., respectively.
Conclusion: The PBPK and DDI models of PER were successfully established, which serve as references for the rational use of this medication in children.
期刊介绍：
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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