title: Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.
abstract: 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.
authors.affiliation: West Virginia University School of Pharmacy, 1124 Health Sciences North, Morgantown, WV.
authors.forename: Marcia D
authors.initials: MD
authors.lastname: Fields
authors.affiliation: West Virginia University School of Pharmacy, 1124 Health Sciences North, Morgantown, WV.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Abate
authors.affiliation: West Virginia University School of Public Health, Morgantown, WV.
authors.forename: Lan
authors.initials: L
authors.lastname: Hu
authors.affiliation: West Virginia University School of Public Health, Morgantown, WV.
authors.forename: D Leann
authors.initials: DL
authors.lastname: Long
authors.affiliation: West Virginia University School of Pharmacy, 1124 Health Sciences North, Morgantown, WV.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Blommel
authors.affiliation: West Virginia Office of the Chief Medical Examiner, Charleston, WV.
authors.forename: Nabila A
authors.initials: NA
authors.lastname: Haikal
authors.affiliation: West Virginia Office of the Chief Medical Examiner, Charleston, WV.
authors.forename: James C
authors.initials: JC
authors.lastname: Kraner
mesh_terms: D000059:Accidents; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000032:analysis / Q000506:poisoning*; D001569:Benzodiazepines / Q000032:analysis / Q000506:poisoning*; D016208:Databases, Factual; D062787:Drug Overdose / Q000401:mortality; D005260:Female; D053593:Forensic Toxicology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000401:mortality*; D014903:West Virginia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D001569:Benzodiazepines
keywords: accidental death; benzodiazepines; cytochrome P-450 enzyme system; drug concentration; drug-drug interactions; forensic science; forensic toxicology; metabolites; narcotics; opioids