Pharmacokinetics and Drug Interaction of Antiepileptic Drugs in Children and Adolescents

Abstract

Selecting the most appropriate antiepileptic drug (AED) or combination of drugs for each patient and identifying the most suitable therapeutic regimen for their needs is increasingly challenging, especially among pediatric populations. In fact, the pharmacokinetics of several drugs vary widely in children with epilepsy because of age-related factors, which can influence the absorption, distribution, metabolism, and elimination of the pharmacological agent. In addition, individual factors, such as seizure type, associated comorbidities, individual pharmacokinetics, and potential drug interactions, may contribute to large fluctuations in serum drug concentrations and, therefore, clinical response. Therapeutic drug concentration monitoring (TDM) is an essential tool to deal with this complexity, enabling the definition of individual therapeutic concentrations and adaptive control of dosing to minimize drug interactions and prevent loss of efficacy or toxicity. Moreover, pharmacokinetic/pharmacodynamic modelling integrated with dashboard systems have recently been tested in antiepileptic therapy, although more clinical trials are required to support their use in clinical practice. We review the mechanism of action, pharmacokinetics, drug-drug interactions, and safety/tolerability profiles of the main AEDs currently used in children and adolescents, paying particular regard to issues of relevance when treating this patient population. Indications for TDM are provided for each AED as useful support to the clinical management of pediatric patients with epilepsy by optimizing pharmacological therapy.

Simultaneous Determination of Phenobarbital, Phenytoin, Carbamazepine and Carbamazepine-10,11-epoxide in Plasma of Epileptic Patients

“…CBZ induces the activity of cytochrome P450 enzymes and its dose adjustment should be done after achievement of autoinduction and before addition of the next drug to the therapeutic regimen. 22 In 22 cases (75.9% of CBZ receivers), PB + CBZ was co-administered. For PB, PHT and CBZ in 78%, 85%, and 82% of the cases, the concentrations were less than therapeutic range in children.…”

“…Differences exist in the pharmacokinetic behavior of drugs between children and adults, also between children in various development steps, and in many cases pediatrics drug dosage is scheduled based on personal experience of the pediatrician. 21 Recent findings on pharmacokinetic and drug interactions of AEDs in children and adolescents was reviewed by Lapadre et al 22 Variations in pH value of gastrointestinal tract, slower gastric emptying, thinner stratum corneum, greater cutaneous perfusion, more hydration of epidermis, reduced skeletal-muscle blood flow, and insufficient muscular contraction may affect drug absorption in pediatrics. 21 Relatively larger total body water and lower fat tissue cause some variations in distribution of drugs in pediatrics.…”

Understanding Childhood Neuroimmune Diseases of the Central Nervous System

“…The management of AGS is generally supportive and symptomatic, with antiepileptic drugs to treat epileptic seizures (149)(150)(151) or botulinum toxin injections or levodopa to manage spasticity and dystonia. Corticosteroids have been shown to lower IFN-α concentrations in CSF and may be of benefit for skin manifestations.…”

Cannabidiol Determination on Peripheral Capillary Blood Using a Microsampling Method and Ultra-High-Performance Liquid Chromatography Tandem Mass Spectrometry with On-Line Sample Preparation

“…Therapeutic drug monitoring (TDM) is helpful in the management of patients with epilepsy for old and new anti-seizure medications (ASMs), often in response to single patient-specific pharmacokinetic or pharmacodynamic issues [1][2][3]. TDM in epilepsy patients is commonly performed on plasma or serum; however, the use of dried plasma spots (DPSs) may facilitate sample shipment to reference laboratories [4,5].…”