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Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative

Zajic, Stefan C.a; Jarvis, Joseph P.a; Zhang, Pana; Rajula, Kaveri D.a; Brangan, Andrewa; Brenner, Ruthb; Dempsey, Michael P.c; Christman, Michael F.a,✠

Pharmacogenetics and Genomics: April 2019 - Volume 29 - Issue 3 - p 49–57
doi: 10.1097/FPC.0000000000000364
ORIGINAL ARTICLES
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Objectives The objectives of this study were to determine whether differences in CYP2C8 and CYP2C9 haplotype influence the dose of ibuprofen self-administered by individuals, and to examine the potential relationship between CYP2C8 and CYP2C9 reduced metabolism haplotypes and adverse events.

Participants and methods We investigated relationships between genetic variations in CYP2C8 and CYP2C9 and ibuprofen use, dose, and side effects (reported by questionnaire) in 445 participants from the Coriell Personalized Medicine Collaborative.

Results Carriers of reduced metabolism haplotypes for CYP2C8 (*2, *3, *4) and CYP2C9 (*2, *3) were significantly (P=0.0171) more likely than those lacking these variants to take less than the recommended dose of ibuprofen, after controlling for sex, age, race, and cohort. In contrast to ibuprofen dose, there were no differences in ibuprofen use frequency or reported side effects based on haplotype. However, there are often no early signs of acute kidney injury, the most serious side effect of elevated ibuprofen exposure.

Conclusion These results suggest a subset of individuals with genetic variation in CYP2C8 and CYP2C9 recognize that they obtain adequate drug efficacy with lower ibuprofen doses, or take lower doses due to prior side effects. However, most (82.6%) individuals with reduced metabolism haplotypes nonetheless took recommended or higher doses, potentially putting them at increased risk for side effects.

aCoriell Institute for Medical Research, Camden, New Jersey

bAir Force Medical Support Agency, Falls Church

cDefense Threat Reduction Agency, Fort Belvoir, Virginia, USA

✠ Deceased.

Correspondence to Stefan C. Zajic, PhD, Coriell Institute for Medical Research, 403 Haddon Avenue, Camden, NJ 08103, USA Tel: +1 856 412 6993; fax: +1 856 964 0254; e-mail: szajic@coriell.org

Received August 9, 2018

Accepted November 5, 2018

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