Document Detail

Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures.
MedLine Citation:
PMID:  22331680     Owner:  NLM     Status:  Publisher    
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.
Soon Min Lee; Jae Yong Chung; Young Mock Lee; Min Soo Park; Ran Namgung; Kook In Park; Chul Lee
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-13
Journal Detail:
Title:  Archives of disease in childhood     Volume:  -     ISSN:  1468-2044     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372434     Medline TA:  Arch Dis Child     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
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