Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?
<h4>Background</h4>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 CYP2C8/2C...
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2010
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oai:doaj.org-article:e242886f71a545b8b390885bb03453e12021-11-18T06:35:49ZAre cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?1932-620310.1371/journal.pone.0012329https://doaj.org/article/e242886f71a545b8b390885bb03453e12010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20808793/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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 DurrmeyerShushanik HovhannisyanYves MédardEvelyne Jacqz-AigrainFabrice DecobertJérome BarreCorinne AlbertiYannick AujardClaude DananOlivier BaudPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12329 (2010) |
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Medicine R Science Q Xavier Durrmeyer Shushanik Hovhannisyan Yves Médard Evelyne Jacqz-Aigrain Fabrice Decobert Jérome Barre Corinne Alberti Yannick Aujard Claude Danan Olivier Baud Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| description |
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
Xavier Durrmeyer Shushanik Hovhannisyan Yves Médard Evelyne Jacqz-Aigrain Fabrice Decobert Jérome Barre Corinne Alberti Yannick Aujard Claude Danan Olivier Baud |
| author_facet |
Xavier Durrmeyer Shushanik Hovhannisyan Yves Médard Evelyne Jacqz-Aigrain Fabrice Decobert Jérome Barre Corinne Alberti Yannick Aujard Claude Danan Olivier Baud |
| author_sort |
Xavier Durrmeyer |
| title |
Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| title_short |
Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| title_full |
Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| title_fullStr |
Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| title_full_unstemmed |
Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants? |
| title_sort |
are cytochrome p450 cyp2c8 and cyp2c9 polymorphisms associated with ibuprofen response in very preterm infants? |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/e242886f71a545b8b390885bb03453e1 |
| work_keys_str_mv |
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