CYP2D6 Expression in Veterans Experiencing Opioid Overdose: A Postmortem Review
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-blind
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 firstname.lastname@example.org
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
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]