Document Detail

Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?
MedLine Citation:
PMID:  20808793     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Patent ductus arteriosus (PDA) in extremely preterm infants remains a challenging condition with conflicting treatment strategies. Ibuprofen is currently used to treat PDA with ductal closure failure rate up to 40%. We test the hypothesis that cytochrome P450 CYP2C8/2C9 polymorphisms may predict ibuprofen response.
METHODOLOGY/PRINCIPAL FINDINGS: We studied extremely preterm neonates with haemodynamically significant PDA and treated with ibuprofen. One or two variant CYP2C8 and/or 2C9 alleles were found in 17% of the population, most of them were from Caucasian ethnicity (67-74%). Response to ibuprofen and clinical course of infants carrying variants CYP2C8 and CYP2C9 were similar. Comparing infants with wild type or variant CYP2C8 and CYP2C9 genotypes, response rate to ibuprofen was significantly higher in wild type than in mutated carriers in univariate analysis (73% versus 52%, p = 0.04). Comparing responders (ductus closure; n = 75) and non-responders (surgical ligation; n = 36), the only two factors significantly associated with the response to ibuprofen using multivariate analysis were higher gestational age and non Caucasian ethnicity but not CYP2C polymorphism.
CONCLUSIONS: CYP2C polymorphism was not associated with PDA response to ibuprofen and this factor appears not appropriate to optimize the ductal closure rate by modulating ibuprofen dosing strategy. This study points out the role for ethnicity in the interindividual variability of response to ibuprofen in extremely preterm infants.
Xavier Durrmeyer; Shushanik Hovhannisyan; Yves Médard; Evelyne Jacqz-Aigrain; Fabrice Decobert; Jérome Barre; Corinne Alberti; Yannick Aujard; Claude Danan; Olivier Baud
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-23
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-11-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e12329     Citation Subset:  IM    
Neonatal Intensive Care Unit, CHI Créteil, France.
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MeSH Terms
Aryl Hydrocarbon Hydroxylases / genetics*
Ductus Arteriosus, Patent / drug therapy,  genetics,  therapy
Ibuprofen / pharmacology*,  therapeutic use
Infant, Newborn
Polymorphism, Single Nucleotide*
Premature Birth*
Treatment Outcome
Reg. No./Substance:
15687-27-1/Ibuprofen; EC Hydrocarbon Hydroxylases; EC protein, human; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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