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CYP2D6 Expression in Veterans Experiencing Opioid Overdose: A Postmortem Review

Authors Boyle J, Stock CJ

Received 13 May 2020

Accepted for publication 20 July 2020

Published 11 August 2020 Volume 2020:13 Pages 289—293


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth

Julia Boyle,1,2 Christopher J Stock1

1Department of Pharmacy, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 2Department of Pharmacy Practice, Idaho State University College of Pharmacy, Meridian, ID, USA

Correspondence: Julia Boyle Email

Purpose: The purpose is to characterize the CYP2D6 genotype and predict the phenotype of decedents of opioid overdose to determine if the ultrarapid (UM) phenotype is over-represented in opioid overdose deaths. CYP2D6 is the enzyme responsible for metabolism of various opioids implicated in overdose. The UM group may be at greater risk for overdose due to the rapid metabolism of hydrocodone, oxycodone, or tramadol to more active/potent metabolites than their peers with (poor) PM, (intermediate) IM, or (extensive) EM metabolic phenotypes.
Patients and Methods: Blood samples obtained during autopsy following an opioid overdose from 75 US military veteran decedents prescribed hydrocodone, oxycodone, or tramadol from one VA medical center were analyzed. DNA extraction, CYP2D6 genotyping, and copy number variation (CNV) testing were performed using the iPLEX® genotyping assay and MassARRAY. Phenotype prediction was based on Clinical Pharmacogenetics Implementation Consortium (CPIC) recommendations. Toxicology results were obtained from Medical Examiner reports of the deceased. Prescription medication information was extracted from archived medical records.
Results: The majority of the sample had a phenotype of EM metabolizer (75%), with 7% of the total sample having a UM metabolizer phenotype. In addition to hydrocodone, oxycodone, and tramadol (found in 41% of opioid positive samples), other opioids found in toxicology tests included diacetylmorphine, fentanyl, buprenorphine, and methadone. Two or more substances, including alcohol, benzodiazepines, and other potentially sedating medications, were found in nearly half of the opioid positive toxicology samples.
Conclusion: In this study, 7% of veteran decedents of opioid overdose had CYP2D6 UM metabolic phenotype. The small sample size precludes a conclusion that the frequency of UM phenotype is greater than expected in North American Caucasian groups. The findings in this study do not support the hypothesis that the UM phenotype is over-represented in opioid overdose.

Keywords: pharmacogenomics, phenotype, mortality, cytochrome P450, drug metabolism, copy number variation

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