Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests.

Autor: Zhu GD; Millennium Health, LLC, San Diego, CA, USA. Dan.Zhu@millenniumhealth.com., Whitley P; Millennium Health, LLC, San Diego, CA, USA., LaRue L; Millennium Health, LLC, San Diego, CA, USA., Adkins B; Millennium Health, LLC, San Diego, CA, USA., Dawson E; Millennium Health, LLC, San Diego, CA, USA., Huskey A; Millennium Health, LLC, San Diego, CA, USA., Capparelli EV; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA., Del Tredici AL; Millennium Health, LLC, San Diego, CA, USA.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2022 Feb; Vol. 22 (1), pp. 25-32. Date of Electronic Publication: 2021 Sep 03.
DOI: 10.1038/s41397-021-00253-5
Abstrakt: Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone. Genetic variation in CYP2D6 and CYP2C19 had a significant impact on oxymorphone/oxycodone ratios, with a 6.9-fold difference between CYP2D6 ultrarapid metabolizers (UMs) and poor metabolizers (PMs; p < 10 -300 ) and a 1.6-fold difference between CYP2C19 UMs and PMs (p = 1.50 × 10 -4 ). CYP2D6 variation also significantly impacted noroxycodone/oxycodone ratios (p = 6.95 × 10 -38 ). Oxycodone-positive specimens from CYP2D6 PMs were ~5-fold more likely to be oxymorphone-negative compared to normal metabolizers. These findings indicate that multivariate analysis of UDT data may be used to reveal the real-world impact of genetic and non-genetic factors on drug metabolism.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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