{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T13:45:33Z","timestamp":1781271933073,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,7,29]],"date-time":"2015-07-29T00:00:00Z","timestamp":1438128000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["1 R49 CE002109"],"award-info":[{"award-number":["1 R49 CE002109"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Forensic Sciences"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Effects of benzodiazepines on postmortem opioid parent and parent\/metabolite blood concentration ratios were determined for fentanyl\u2010, hydrocodone\u2010, methadone\u2010, or oxycodone\u2010related 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\u2010intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.01) compared to hydrocodone alone. The methadone parent\/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). 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.<\/jats:p>","DOI":"10.1111\/1556-4029.12807","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T01:53:16Z","timestamp":1438307596000},"page":"950-956","source":"Crossref","is-referenced-by-count":14,"title":["Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations<sup>,<\/sup><sup>,<\/sup>"],"prefix":"10.1111","volume":"60","author":[{"given":"Marcia D.","family":"Fields","sequence":"first","affiliation":[{"name":"West Virginia University School of Pharmacy 1124 Health Sciences North Morgantown WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Abate","sequence":"additional","affiliation":[{"name":"West Virginia University School of Pharmacy 1124 Health Sciences North Morgantown WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Hu","sequence":"additional","affiliation":[{"name":"West Virginia University School of Public Health Morgantown WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Leann","family":"Long","sequence":"additional","affiliation":[{"name":"West Virginia University School of Public Health Morgantown WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Blommel","sequence":"additional","affiliation":[{"name":"West Virginia University School of Pharmacy 1124 Health Sciences North Morgantown WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabila A.","family":"Haikal","sequence":"additional","affiliation":[{"name":"West Virginia Office of the Chief Medical Examiner Charleston WV"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Kraner","sequence":"additional","affiliation":[{"name":"West Virginia Office of the Chief Medical Examiner Charleston WV"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2008.802"},{"key":"e_1_2_6_3_1","first-page":"1","article-title":"Vital signs: overdoses of prescription opioid pain relievers \u2013 United States 1999\u20132008","volume":"60","author":"Paulozzi LJ","year":"2011","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_6_4_1","unstructured":"National Center for Health Statistics.NCHS data on drug poisoning deaths [Internet]. Atlanta: Centers for Disease Control and Prevention; Updated October 2014;http:\/\/www.cdc.gov\/nchs\/data\/factsheets\/factsheet_drug_poisoning.pdf(accessed May 27 2015)."},{"issue":"12","key":"e_1_2_6_5_1","first-page":"234","article-title":"Number of deaths from poisoning, drug poisoning, and drug poisoning involving opioid analgesics \u2013 United States, 1999\u20132010. QuickStats","volume":"62","author":"Chen LH","year":"2013","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_6_6_1","first-page":"1","article-title":"Increase in fatal poisonings involving opioid analgesics in the United States, 1999\u20132006","volume":"22","author":"Warner M","year":"2009","journal-title":"NCHS Data Brief"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/30.8.603"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1520\/JFS2004194"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1520\/JFS2002323"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(03)00033-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1556-4029.2009.01278.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1520\/JFS2003221"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000433-200209000-00021"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2009.02650.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1556-4029.2010.01408.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/27.2.57"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1197\/j.aem.2005.12.011"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1556-4029.2007.00565.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/32.2.165"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(97)00068-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/24.7.627"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(03)00057-4"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bkr013"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2012.07.011"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2010.11.007"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05567blu"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.07.004"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199601000-00031"},{"issue":"9","key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/S0090-9556(25)07486-0","article-title":"Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4","volume":"24","author":"Feierman DE","year":"1996","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(02)00856-5"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.02002.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jflm.2008.08.002"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.10303"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.6.742"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.4.447"},{"key":"e_1_2_6_36_1","unstructured":"Pharmacist's Letter Detail\u2010Document.Cytochrome P450 drug interactions. Pharmacist's Letter\/Prescriber's Letter 2013 Oct."},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4637.2009.00596.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.01.023"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90051-0"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00673.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0893-3"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0376-8716(86)90051-7"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1982.22"},{"key":"e_1_2_6_44_1","unstructured":"DAWN Mortality Data State Profiles West Virginia [Internet]. Rockville MD: Center for Behavioral Health Statistics and Quality 2010;http:\/\/www.samhsa.gov\/data\/2k12\/DAWNMEAnnualReport2010\/DAWN-ME-AnnualReport2010-208-WV.htm(accessed May 27 2015)."},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/28.7.616"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2010.06.015"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/33.8.423"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1520\/JFS14088J"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-010-0948-5"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/34.8.476"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1191\/0960327102ht303oa"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2012.03.016"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/ewjm.172.1.11"},{"key":"e_1_2_6_54_1","unstructured":"KranerJC ClayDJ GebhardtMA KaplanJA.Methadone to metabolite ratio in cases of fatal overdose. In: Proceedings of the American Academy of Forensic Sciences; 2006 Feb 20\u201325; Seattle WA. Colorado Springs CO: American Academy of Forensic Sciences 2006;346."},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2010.07.011"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(03)00159-2"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2010.00274.x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2004.02.013"}],"container-title":["Journal of Forensic Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1556-4029.12807","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1556-4029.12807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T20:39:58Z","timestamp":1748551198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1556-4029.12807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1111\/1556-4029.12807"],"URL":"https:\/\/doi.org\/10.1111\/1556-4029.12807","archive":["Portico"],"relation":{},"ISSN":["0022-1198","1556-4029"],"issn-type":[{"value":"0022-1198","type":"print"},{"value":"1556-4029","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7]]}}}