Related Experiment Video

Updated: Jul 2, 2025

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization
09:57

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization

Published on: September 20, 2024

2.6K

Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With

Huijuan Wang1,2, Junyan Wang1, Bin Lin3,4

  • 1Department of Pharmacy, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Journal of Clinical Pharmacology
|February 21, 2024
PubMed

Insights

Perampanel (PER) exposure varies significantly in children with epilepsy. Younger age, enzyme inducers, valproic acid, and CYP3A5*3 genotype influence PER levels, impacting treatment effectiveness.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Genetics

Background:

  • Perampanel (PER) is an antiseizure medication with significant inter-individual variability in pediatric plasma concentrations.
  • Understanding factors influencing PER exposure is crucial for optimizing treatment in children with epilepsy.

Purpose of the Study:

  • To investigate the impact of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on Perampanel exposure in Chinese pediatric epilepsy patients.

Main Methods:

  • Retrospective analysis of clinical data from 135 pediatric patients (178 blood samples) treated between January 2021 and December 2022.
  • Investigated factors influencing Perampanel's daily dose, plasma concentration, and concentration-to-dose ratio (CDR).
  • Analyzed the effects of age groups, enzyme inducers, valproic acid, and CYP3A4/5 genotypes (CYP3A5*3, CYP3A4*1G).

Main Results:

  • Younger age (<4 years) was associated with significantly decreased PER CDR (48.0% and 39.1% lower than older groups).
  • Enzyme inducers reduced PER CDR by 34.5%, while valproic acid increased it by 71.7%.
  • CYP3A5*3/*3 genotype carriers showed a 21.5% increase in PER CDR compared to CYP3A5*1/*3 expressers; no correlation with CYP3A4*1G.

Conclusions:

  • Perampanel exhibits substantial inter-individual variability in pediatric plasma concentrations.
  • Age, specific comedications (enzyme inducers, valproic acid), and CYP3A5*3 genotype are significant predictors of PER exposure in pediatric epilepsy patients.

Keywords:
concentration‐to‐dose ratiodrug–drug interactionepilepsypediatricperampanelpolymorphisms

More Related Videos

Electrophoretic Delivery of &#947;-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice07:01

Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice

Published on: May 16, 2019

9.1K
Pentylenetetrazole-Induced Kindling Mouse Model07:06

Pentylenetetrazole-Induced Kindling Mouse Model

Published on: June 12, 2018

33.1K

Related Concept Videos

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
137
Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
2.0K
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
183
Antiepileptic Drugs: Glutamate Antagonists01:14

Antiepileptic Drugs: Glutamate Antagonists

Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
355
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response01:15

Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
61
Factors Affecting Protein-Drug Binding: Patient-Related Factors01:29

Factors Affecting Protein-Drug Binding: Patient-Related Factors

Protein-drug binding, a pivotal aspect of pharmacokinetics, is subject to considerable variability influenced by an array of patient-related factors. The intricate interplay of age, individual differences, and pathological conditions significantly impact the binding dynamics and subsequent pharmacological effects.
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
59