Pharmacokinetic variability of antiepileptic drugs in neonates: A narrative review

Year 2025, Volume: 13 Issue: 2, 48 - 55, 31.07.2025

Mamatha Rejeev , Princy Palatty Tanya Thomas Laxmi Govindraj

https://doi.org/10.21765/pprjournal.1671754

Abstract

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.

Keywords

antiepileptic drugs , neonatal seizures , pharmacokinetics , newborn , variability

Yenidoğanlarda antiepileptik ilaçların farmakokinetik değişkenliği

Abstract

Arka Plan:
Neonatal nöbetler, önemli bir klinik zorluk teşkil eder ve görülme sıklığında belirgin sosyoekonomik farklılıklar vardır. Yüksek gelirli ülkelerde 1.000 canlı doğumda 1-3 oranında görülürken, düşük ve orta gelirli ülkelerde bu oran 1.000 doğumda 36-90’a kadar çıkabilmektedir. Yenidoğanlar, hızla değişen fizyolojileri nedeniyle farmakolojik açıdan benzersiz zorluklar sunar; bu durum antiepileptik ilaç uygulamalarında dikkatli değerlendirmeyi gerektirir.

Amaç:
Bu derleme, yenidoğan ve bebeklerde antiepileptik ilaçların farmakokinetik değişkenliğini analiz ederek, doza bağlı advers reaksiyonlara katkıda bulunan faktörleri ve bireyselleştirilmiş dozlama yaklaşımlarının önemini anlamayı amaçlamaktadır.

Yöntem:
PubMed, Embase, Cochrane Library ve Medscape gibi çeşitli elektronik veritabanlarında mevcut literatürün kapsamlı bir taraması yapılmıştır. Tarama, yenidoğanlarda antiepileptik ilaçların farmakokinetik özellikleri, fizyolojik faktörlerin etkisi, terapötik müdahaleler ve uzun vadeli nörolojik sonuçlar üzerine odaklanmıştır. Özellikle terapötik hipotermi ve diğer yoğun bakım müdahalelerinin ilaç dağılımı üzerindeki etkilerine özel önem verilmiştir.

Bulgular:
Yenidoğan fizyolojisi, antiepileptik ilaçların dağılımını; dağılım hacmi, eliminasyon, protein bağlanması ve enzim aktivitesindeki değişiklikler gibi birçok mekanizma aracılığıyla önemli ölçüde etkiler. Özellikle hipoksik-iskemik ensefalopatide kullanılan terapötik hipotermi gibi müdahaleler, farmakokinetik parametreleri ve ilaç eliminasyonunu önemli ölçüde değiştirebilir. Hayvan çalışmaları, erken dönemde antiepileptik ilaç maruziyetinin nörogelişimsel etkileri olabileceğini öne sürmektedir; ancak nöbetlerin beyin gelişimi üzerindeki eş zamanlı etkileri nedeniyle doğrudan nedensellik kurmak zordur.

Sonuç:
Yenidoğanların kendine özgü fizyolojik özellikleri, antiepileptik ilaç dozlamasında bireyselleştirilmiş yaklaşımları zorunlu kılmaktadır. Gelişimsel faktörler, terapötik müdahaleler ve ilaç dağılımı arasındaki karmaşık etkileşim, dikkatli izlem ve hasta özelinde doz ayarlamalarının önemini vurgulamaktadır. Erken dönemde antiepileptik ilaç maruziyetinin uzun vadeli nörogelişimsel etkilerini daha iyi anlamak için ileri araştırmalara ihtiyaç vardır.

Keywords

Antiepileptik ilaçlar , neonatal nöbetler , farmakokinetik , yenidoğan , değişkenlik

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