Pharmacokinetic variability of antiepileptic drugs in neonates: A narrative review

Background:Neonatal seizures represent a significant clinical challenge with marked socioeconomic disparities in prevalence, ranging from 1-3 per 1,000 live births in high-income nations to 36-90 per 1,000 in low- and middle-income countries. Neonates present unique pharmacological challenges due to their rapidly changing physiology, requiring careful consideration in antiepileptic drug administration. Purpose:This review analyzes the pharmacokinetic variability of antiepileptic drugs in neonates and infants, understanding the factors that contribute to dose-dependent adverse reactions and the importance of individualized dosing approaches. Methods:A comprehensive review of current literature was conducted across multiple electronic databases including PubMed, Embase, Cochrane Library and Medscape examining the pharmacokinetic properties of antiepileptic medications in neonates, impact of physiological factors, therapeutic interventions, and long-term neurological consequences. Special attention was given to the effects of therapeutic hypothermia and other intensive care interventions on drug disposition. Results:Neonatal physiology significantly impacts antiepileptic drug disposition through multiple mechanisms, including variations in distribution, clearance, protein binding, and enzyme activity. Therapeutic interventions, particularly hypothermia in hypoxic-ischemic encephalopathy, can substantially alter pharmacokinetic parameters and drug clearance. Animal studies suggest potential neurodevelopmental impacts of early antiepileptic drug exposure, though establishing direct causality remains challenging due to the concurrent effects of seizures on brain development.Conclusion: The unique physiological characteristics of neonates necessitate an individualized approach to antiepileptic drug dosing. The complex interplay between developmental factors, therapeutic interventions, and drug disposition highlights the importance of careful monitoring and dose adjustment based on patient-specific factors. Further research is needed to better understand the long-term neurodevelopmental implications of early antiepileptic drug exposure.