Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures

Archives of Disease in Childhood
Soon Min LeeChul Lee

Abstract

Phenobarbital (PB), commonly used as the preferred treatment for neonatal seizure, is a drug that requires careful dose adjustments based on therapeutic drug monitoring. It has been reported that PB metabolism was affected by cytochrome P450 (CYP)2C19 polymorphisms in adults requiring dose adjustment. This study aimed to evaluate the effects of CYP2C19 genetic polymorphisms on PB pharmacokinetics (PK) in neonates and infants with seizures. CYP2C19 (wild type: CYP2C19*1/*1, heterozygous extensive metabolisers: CYP2C19*1/*2, *1/*3 and poor metabolisers: CYP2C19*2/*2, *2/*3) genetic polymorphisms in 52 neonates and infants with seizures were analysed. PK parameters were compared based on genotypes. The NONMEM program was used for population PK modelling. No significant difference in PB clearance (CL), volume of distribution (Vd) and concentrations were shown among the CYP2C19 genotype groups. The results of PK modelling were as follows: Vd=3590 ×(body weight (BWT)/4)(0.766) ×(AGE/2)(0.283) and CL=32.6 × (BWT/4)(1.21). PB PK parameters of neonates and infants with seizures were not significantly different among the groups with different CYP2C19 genotypes. The addition of CYP2C19 genotyping to PK models did not improve the dosing st...Continue Reading

Citations

Apr 5, 2013·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Wiparat ManuyakornSuwat Benjaponpitak
Apr 8, 2015·Journal of Clinical Pharmacy and Therapeutics·T KeangpraphunP Kijsanayotin
Jun 14, 2018·Epilepsia·Brady S MoffettSimon Y Kayyal
Sep 25, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yun-Chen TienXiao-Bo Zhong
Apr 1, 2020·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·Céline ThibaultAthena F Zuppa
Oct 14, 2020·Expert Opinion on Drug Metabolism & Toxicology·Matthijs W van HoogdalemTomoyuki Mizuno
Oct 21, 2020·European Journal of Clinical Pharmacology·Janthima Methaneethorn, Nattawut Leelakanok

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