{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:59:59Z","timestamp":1785373199957,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008673","name":"Center for AIDS Research, University of California, San Diego","doi-asserted-by":"publisher","award":["P30 AI036214"],"award-info":[{"award-number":["P30 AI036214"]}],"id":[{"id":"10.13039\/100008673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA062278"],"award-info":[{"award-number":["DA062278"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AI169609"],"award-info":[{"award-number":["P01 AI169609"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA055491"],"award-info":[{"award-number":["R01 DA055491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Although opioids are central to end of life (EoL) care, tissue\u2010level opioid exposure remains poorly understood. The objective of this study was to characterize the relationship between prescription\u2010derived morphine equivalent daily dose (MEDD) and measured morphine concentrations across multiple organs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We analysed data from the\n                      <jats:italic>Last Gift<\/jats:italic>\n                      cohort, a community\u2010centred HIV research rapid autopsy programme. Cumulative MEDD for the final 7 and 30\u2009days before death (MEDD\u20107, MEDD\u201030) was calculated using prescription data. Postmortem samples from multiple organs were analysed using ultra\u2010high\u2010performance liquid chromatography with tandem mass spectrometry to quantify opioids. Mixed\u2010effects regression models and Pearson correlations evaluated relationships between MEDD and tissue morphine concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Among 261 samples from 27 participants (median age 65\u2009years), 96% had \u22651 detectable opioid. Morphine was most frequently prescribed (78%), followed by fentanyl (41%), hydromorphone (37%), and oxycodone (33%). Median MEDD\u20107 and MEDD\u201030 were 940 (IQR 158\u20133481) and 3430 (IQR 563\u20139972), respectively. Morphine concentrations were highest in the ascending colon, kidney, duodenum, and liver, and lowest in adipose tissue and cerebrospinal fluid. Tissue morphine concentrations correlated with both MEDD\u20107 and MEDD\u201030 (e.g., medulla\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009.80; spinal cord\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009.77; parietal cortex\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009.72; all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01). In adjusted mixed\u2010effects models, each 10\u2010fold increase in MEDD\u20107\/\u201030 predicted a 3.7\u2010 to 3.8\u2010fold increase in tissue morphine concentration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Prescription\u2010based morphine exposure was strongly associated with morphine tissue concentrations across multiple organs, providing a quantitative framework for integrating pharmacologic data into EoL research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70535","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:30:04Z","timestamp":1774927804000},"page":"2624-2635","source":"Crossref","is-referenced-by-count":0,"title":["Mapping opioid exposure through prescription data and postmortem analysis of opioid drugs in multiple tissues"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-5209","authenticated-orcid":false,"given":"Niamh","family":"Higgins","sequence":"first","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice and Sciences University of California San Diego  La Jolla California USA"},{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Wells","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0921-549X","authenticated-orcid":false,"given":"Nimish","family":"Patel","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice and Sciences University of California San Diego  La Jolla California USA"},{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Muttera","sequence":"additional","affiliation":[{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Trunfio","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Manca","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amedeo","family":"De Nicol\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0377-9630","authenticated-orcid":false,"given":"Micol","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bonora","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Cusato","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Palermiti","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1321-4126","authenticated-orcid":false,"given":"Antonio","family":"D'Avolio","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences University of Turin, Amedeo di Savoia Hospital  Turin Italy"},{"name":"CoQua Lab s.r.l.  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Borochoff","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia K.","family":"Riggs","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6968","authenticated-orcid":false,"given":"Elizabeth","family":"Hastie","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia S.","family":"Atayee","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmacy Practice and Sciences University of California San Diego  La Jolla California USA"},{"name":"Department of Pharmacy UC San Diego Health  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Solso","sequence":"additional","affiliation":[{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Dullano","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Gomez\u2010Moreno","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Tenenbaum","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Deiss","sequence":"additional","affiliation":[{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"},{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davey M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Antiviral Research Center (AVRC) University of California San Diego  San Diego California USA"},{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Chaillon","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Global Public Health, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"CDC Guideline for Prescribing Opioids for Chronic Pain\u2010United States 2016 Morbidity and Mortality Weekly Report [Internet].2016. 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