Pharmacokinetic considerations for anti-epileptic drugs in children

ABSTRACT

Introduction: Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored.

Areas covered: Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity) can significantly modify the pharmacokinetic profile of AEDs (adsorption, volume of distribution, half-life, clearance), leading to an altered treatment response. We reviewed the main pharmacokinetic characteristics of AEDs used in children, focusing on age-related factors which are of relevance when treating this patient population.

Expert opinion: To deal with this pharmacokinetic variability, physicians have at their disposal two tools: 1) therapeutic drug concentration monitoring, which may help to set the optimal therapeutic regimen for each patient and to monitor eventual fluctuation, and 2) the use of extended-release drug formulations, when available. In the next future, the development of ‘ad-hoc’ electronic dashboard systems will represent relevant decision-support tools making the AED therapy even more individualized and precise, especially in children.

KEYWORDS:

• Pharmacokinetics
• antiepileptic drugs
• children
• neonates
• epilepsy
• therapy
• paediatric
• therapeutic drug monitoring
• metabolism
• clearance

Article highlights

• Physiological changes occurring during development age (different body composition, immature metabolic patterns, reduced renal activity), can significantly affect the pharmacokinetic profile of many AEDs

• Young children show increased capacity of metabolizing AEDs, and thus require larger dosages per kg.

• Neonates tend to show reduced clearance and capacity of metabolizing AEDs, and thus require lower dosages per kg.

• Inter- and intra-individual variability of AEDs pharmacokinetic depend on both age-related and genetic factors

• Therapeutic drug concentration monitoring will help to individuate the most appropriate dosing regimen for each patient

• Pharmacokinetic data referring to the use of AEDs in pediatric population, are reported in detail in an appropriate table which provides an easy to use lookup.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.