Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl‐, hydrocodone‐, methadone‐, or oxycodone‐related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diaz...

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Bibliographic Details
Published in:Journal of forensic sciences 2015-07, Vol.60 (4), p.950-956
Main Authors: Fields, Marcia D., Abate, Marie A., Hu, Lan, Long, D. Leann, Blommel, Matthew L., Haikal, Nabila A., Kraner, James C.
Format: Article
Language:English
Subjects:
accidental death
Accidents
Adult
Aged
Analgesics, Opioid - analysis
Analgesics, Opioid - poisoning
benzodiazepines
Benzodiazepines - analysis
Benzodiazepines - poisoning
cytochrome P-450 enzyme system
Databases, Factual
drug concentration
Drug overdose
Drug Overdose - mortality
drug-drug interactions
Female
forensic science
Forensic sciences
Forensic Toxicology
Humans
Male
Metabolites
Middle Aged
Narcotics
Opioid-Related Disorders - mortality
opioids
West Virginia - epidemiology
Young Adult
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Summary:Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl‐, hydrocodone‐, methadone‐, or oxycodone‐related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co‐intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored.
ISSN:0022-1198
1556-4029
DOI:10.1111/1556-4029.12807