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

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. ✠ Deceased. Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government. 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 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2SaYkDC
via IFTTT