دورية أكاديمية
CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose.
| العنوان: | CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose. |
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| المؤلفون: | Whitt AG; Department of Pathology and Laboratory Medicine, 5170 University of Louisville School of Medicine , Louisville, KY, USA., Jortani SA; Department of Pathology and Laboratory Medicine, 5170 University of Louisville School of Medicine , Louisville, KY, USA. |
| المصدر: | Drug metabolism and personalized therapy [Drug Metab Pers Ther] 2024 May 14; Vol. 39 (2), pp. 99-102. Date of Electronic Publication: 2024 May 14 (Print Publication: 2024). |
| نوع المنشور: | Case Reports; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: De Gruyter Country of Publication: Germany NLM ID: 101653409 Publication Model: eCollection Cited Medium: Internet ISSN: 2363-8915 (Electronic) Linking ISSN: 23638915 NLM ISO Abbreviation: Drug Metab Pers Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin : De Gruyter, [2015]- |
| مواضيع طبية MeSH: | Hydrocodone*/poisoning , Diphenhydramine*/poisoning , Drug Overdose* , Cytochrome P-450 CYP2D6 Inhibitors* , Analgesics, Opioid*/poisoning, Humans ; Female ; Middle Aged ; Cytochrome P-450 CYP2D6/metabolism ; Fatal Outcome ; Acetaminophen/poisoning |
| مستخلص: | Objectives: Fatal drug overdoses often involve multiple co-intoxicants, including opioids. Hydrocodone, the most prescribed opioid for pain management, is metabolized to the active metabolite hydromorphone by hepatic CYP2D6. Inhibition of CYP2D6 by other compounds can disrupt the analgesic properties of hydrocodone and extend its half-life. Diphenhydramine is an over-the-counter cold medication and is known to inhibit CYP2D6 activity. Case Presentation: A woman in her late 50s was prescribed hydrocodone/acetaminophen (Norco ® 10/325). Days before her death, she began taking diphenhydramine for cold symptoms. A post-mortem toxicology report detected the following compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (24 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone was not detected (<2 ng/mL). All compounds were detected in therapeutic concentrations, except for hydrocodone, which was present at lethal concentrations. Conclusions: This case highlights a fatal drug-drug interaction between hydrocodone and diphenhydramine. The estimated total body burden of hydrocodone was 6- to 12-fold higher than acetaminophen, which is unexpected, as these two drugs were administered as a single formulation and have similar half-lives. Furthermore, hydromorphone was undetectable. Taken together, these findings are highly suggestive of a fatal opioid overdose precipitated by diphenhydramine. (© 2024 Walter de Gruyter GmbH, Berlin/Boston.) |
| References: | Akutsu, T, Kobayashi, K, Sakurada, K, Ikegaya, H, Furihata, T, Chiba, K. Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos 2007;35:72–8. https://doi.org/10.1124/dmd.106.012088 . (PMID: 10.1124/dmd.106.012088) Dinwiddie, AT, Tanz, LJ, Bitting, J. Notes from the field: antihistamine positivity and involvement in drug overdose deaths - 44 jurisdictions, United States, 2019–2020. MMWR Morb Mortal Wkly Rep 2022;71:1308–10. https://doi.org/10.15585/mmwr.mm7141a4 . (PMID: 10.15585/mmwr.mm7141a4) Goodman, LS, Brunton, LL, Chabner, B, Knollmann, BC. Goodman & Gilman’s pharmacological basis of therapeutics [Internet] . 12th ed. New York: McGraw-Hill; 2011:2084 p. Available from: http://catdir.loc.gov/catdir/enhancements/fy1011/2010000236-t.html [cited 2023 Apr 21]. DePriest, AZ, Puet, BL, Holt, AC, Roberts, A, Cone, EJ. Metabolism and disposition of prescription opioids: a review. Forensic Sci Rev 2015;27:115–45. Schulz, M, Iwersen-Bergmann, S, Andresen, H, Schmoldt, A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care 2012;16:R136. https://doi.org/10.1186/cc11441 . (PMID: 10.1186/cc11441) Molina, DK, Hargrove, VM. What is the lethal concentration of hydrocodone? A comparison of postmortem hydrocodone concentrations in lethal and incidental intoxications. Am J Forensic Med Pathol 2011;32:108–11. https://doi.org/10.1097/paf.0b013e3181dd5a75 . (PMID: 10.1097/paf.0b013e3181dd5a75) Yarema, MC, Becker, CE. Key concepts in postmortem drug redistribution. Clin Toxicol 2005;43:235–41. https://doi.org/10.1081/clt-200058950 . (PMID: 10.1081/clt-200058950) Brockbals, L, Staeheli, SN, Gascho, D, Ebert, LC, Kraemer, T, Steuer, AE. Time-dependent postmortem redistribution of opioids in blood and alternative matrices. J Anal Toxicol 2018;42:365–74. https://doi.org/10.1093/jat/bky017 . (PMID: 10.1093/jat/bky017) Han, E, Kim, E, Hong, H, Jeong, S, Kim, J, In, S, et al.. Evaluation of postmortem redistribution phenomena for commonly encountered drugs. Forensic Sci Int 2012;219:265–71. https://doi.org/10.1016/j.forsciint.2012.01.016 . (PMID: 10.1016/j.forsciint.2012.01.016) Flockhart, D, Thacker, D, McDonald, C, Desta, Z. The Flockhart cytochrome P450 drug-drug interaction table [Internet] ; 2021. Available from: https://drug-interactions.medicine.iu.edu/MainTable.aspx [cited 2023 Dec 14]. Lippold, KM, Jones, CM, Olsen, EO, Giroir, BP. Racial/ethnic and age group differences in opioid and synthetic opioid-involved overdose deaths among adults aged ≥18 years in metropolitan areas - United States, 2015–2017. MMWR Morb Mortal Wkly Rep 2019;68:967–73. https://doi.org/10.15585/mmwr.mm6843a3 . (PMID: 10.15585/mmwr.mm6843a3) |
| فهرسة مساهمة: | Keywords: CYP2D6; diphenhydramine; drug-drug interaction; hydrocodone; opioid overdose |
| المشرفين على المادة: | 6YKS4Y3WQ7 (Hydrocodone) 8GTS82S83M (Diphenhydramine) 0 (Cytochrome P-450 CYP2D6 Inhibitors) 0 (Analgesics, Opioid) EC 1.14.14.1 (Cytochrome P-450 CYP2D6) 362O9ITL9D (Acetaminophen) |
| تواريخ الأحداث: | Date Created: 20240514 Date Completed: 20240729 Latest Revision: 20240731 |
| رمز التحديث: | 20240801 |
| DOI: | 10.1515/dmpt-2023-0081 |
| PMID: | 38741525 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2363-8915 |
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| DOI: | 10.1515/dmpt-2023-0081 |