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. 2019 Aug;20(13):939-946.
doi: 10.2217/pgs-2019-0079.

CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

Sydney R Rooney  1 , Elaine L Shelton  2 , Ida Aka  2 , Christian M Shaffer  3 , Ronald I Clyman  4 , John M Dagle  5 , Kelli Ryckman  6 , Tamorah R Lewis  7 , Jeff Reese  2 , Sara L Van Driest  2   3 , Prince J Kannankeril  2
Affiliations

CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

Sydney R Rooney et al. Pharmacogenomics. 2019 Aug.

Abstract

Aims: To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). Patients & Methods: This is a multicenter cohort study of 144 preterm infants (22-32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention. Results: In multivariate analysis, gestational age (AOR 0.76, 95% CI 0.60-0.96), surfactant use (AOR 9.77, 95% CI 1.15-83.26), and CYP2C9*2 (AOR 3.74; 95% CI 1.34-10.44) were each associated with indomethacin failure. Conclusion: Age, surfactant use, and CYP2C9*2 influence indomethacin treatment outcome in preterm infants with PDA. This combination of clinical and genetic factors may facilitate targeted indomethacin use for PDA.

Keywords: ductus arteriosus; genetics; indomethacin; newborn; pharmacogenomics.

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Conflict of interest statement

Financial & competing interests disclosure

Supported in part by grants: NIH R21 HL132805 to EL Shelton; NIH R01 HL109199 to RI Clyman; NIH R01 HL128386 to J Reese; Burroughs Wellcome 1015006 to SL Van Driest; NIH R01 HD 084461 to PJ Kannankeril. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. The figure shows a Forest plot with multivariate adjusted odds ratio and 95% CI for indomethacin failure resulting in ligation (OR > 1) for estimated gestational age, postnatal age at treatment, sex, surfactant use and the CYP2C9*2 variant.
See this image and copyright information in PMC

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