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

Authors
 Soon Min Lee  ;  Jae Yong Chung  ;  Young Mock Lee  ;  Min Soo Park  ;  Ran Namgung  ;  Kook In Park  ;  Chul Lee 
Citation
 ARCHIVES OF DISEASE IN CHILDHOOD, Vol.97(6) : 569-572, 2012 
Journal Title
ARCHIVES OF DISEASE IN CHILDHOOD
ISSN
 0003-9888 
Issue Date
2012
MeSH
Aryl Hydrocarbon Hydroxylases/genetics* ; Cytochrome P-450 CYP2C19 ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Phenobarbital/pharmacokinetics* ; Phenobarbital/therapeutic use ; Polymorphism, Genetic ; Seizures/drug therapy ; Seizures/metabolism*
Keywords
Aryl Hydrocarbon Hydroxylases/genetics* ; Cytochrome P-450 CYP2C19 ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Phenobarbital/pharmacokinetics* ; Phenobarbital/therapeutic use ; Polymorphism, Genetic ; Seizures/drug therapy ; Seizures/metabolism*
Abstract
BACKGROUND: 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.

AIM: This study aimed to evaluate the effects of CYP2C19 genetic polymorphisms on PB pharmacokinetics (PK) in neonates and infants with seizures.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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 strategies in neonates and infants.
Full Text
http://adc.bmj.com/content/97/6/569.long
DOI
22331680
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Namgung, Ran(남궁란) ORCID logo https://orcid.org/0000-0001-7182-9535
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Park, Min Soo(박민수) ORCID logo https://orcid.org/0000-0002-4395-9938
Lee, Soon Min(이순민) ORCID logo https://orcid.org/0000-0003-0174-1065
Lee, Young Mock(이영목) ORCID logo https://orcid.org/0000-0002-5838-249X
Lee, Chul(이철)
Chung, Jae Yong(정재용)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89606
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