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Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

Xavier Durrmeyer1, Shushanik Hovhannisyan, Yves Médard

  • 1Neonatal Intensive Care Unit, CHI Créteil, France.

Plos One
|September 3, 2010
PubMed

Insights

Genetic variations in CYP2C8/2C9 did not predict ibuprofen response in extremely preterm infants with patent ductus arteriosus (PDA). Ethnicity, not CYP2C polymorphism, influenced treatment outcomes for PDA closure.

Area of Science:

  • Neonatalogy
  • Pharmacogenetics
  • Cardiology

Background:

  • Patent ductus arteriosus (PDA) in extremely preterm infants presents treatment challenges, with ibuprofen showing up to 40% failure rate.
  • Current treatment strategies for PDA are debated, necessitating further investigation into response predictors.
  • Cytochrome P450 (CYP) enzyme polymorphisms are explored for their potential role in predicting drug efficacy.

Purpose of the Study:

  • To investigate the hypothesis that CYP2C8/2C9 gene polymorphisms may predict ibuprofen response in extremely preterm neonates with PDA.
  • To identify factors influencing interindividual variability in ibuprofen efficacy for PDA closure.
  • To evaluate the clinical relevance of CYP2C polymorphisms in optimizing PDA treatment.

Main Methods:

  • Study included extremely preterm neonates diagnosed with hemodynamically significant PDA and treated with ibuprofen.
  • Genotyping for CYP2C8 and CYP2C9 alleles was performed.
  • Infants were categorized based on genotype (wild type vs. variant) and response to ibuprofen (ductal closure vs. surgical ligation).

Main Results:

  • CYP2C8/2C9 variant alleles were present in 17% of the study population, predominantly of Caucasian ethnicity.
  • Univariate analysis showed a significantly higher ibuprofen response rate in infants with wild-type CYP2C genotypes (73%) compared to variant carriers (52%, p=0.04).
  • Multivariate analysis identified higher gestational age and non-Caucasian ethnicity as significant factors associated with ibuprofen response, while CYP2C polymorphism was not.

Conclusions:

  • CYP2C gene polymorphism was not found to be associated with PDA response to ibuprofen in this cohort.
  • The findings suggest that CYP2C polymorphisms are not suitable for optimizing ibuprofen dosing strategies to improve ductal closure rates.
  • Ethnicity appears to play a significant role in the interindividual variability of ibuprofen response in extremely preterm infants.
Abstract

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