{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:04:29Z","timestamp":1788537869548,"version":"build-2803163510"},"reference-count":29,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100021069","name":"Indivior Inc.","doi-asserted-by":"crossref","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100021069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Potent synthetic opioids, such as fentanyl, are increasingly abused, resulting in unprecedented numbers of fatalities from respiratory depression. Treatment with the high-affinity mu-opioid receptor partial agonist buprenorphine may prevent fatalities by reducing binding of potent opioids to the opioid receptor, limiting respiratory depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>To characterize buprenorphine-fentanyl interaction at the level of the mu-opioid receptor in 2 populations (opioid-naive individuals and individuals who chronically use high-dose opioids), the effects of escalating i.v. fentanyl doses with range 0.075\u20130.35 mg\/70 kg (opioid naive) and 0.25\u20130.70 mg\/70 kg (chronic opioid use) on iso-hypercapnic ventilation at 2\u20133 background doses of buprenorphine (target plasma concentrations range: 0.2\u20135 ng\/mL) were quantified using receptor association\/dissociation models combined with biophase distribution models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Buprenorphine produced mild respiratory depression, while high doses of fentanyl caused pronounced respiratory depression and apnea in both populations. When combined with fentanyl, buprenorphine produced a receptor binding\u2013dependent reduction of fentanyl-induced respiratory depression in both populations. In individuals with chronic opioid use, at buprenorphine plasma concentrations of 2 ng\/mL or higher, a protective effect against high-dose fentanyl was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Overall, the results indicate that when buprenorphine mu-opioid receptor occupancy is sufficiently high, fentanyl is unable to activate the mu-opioid receptor and consequently will not cause further respiratory depression in addition to the mild respiratory effects of buprenorphine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>Trialregister.nl, no. NL7028 (https:\/\/www.trialregister.nl\/trial\/7028)<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Indivior Inc., North Chesterfield, Virginia, USA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.156973","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T12:01:16Z","timestamp":1647950476000},"source":"Crossref","is-referenced-by-count":39,"title":["Modeling buprenorphine reduction of fentanyl-induced respiratory depression"],"prefix":"10.1172","volume":"7","author":[{"given":"Erik","family":"Olofsen","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke Hyke","family":"Algera","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-0553","authenticated-orcid":true,"given":"Laurence","family":"Moss","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-4425","authenticated-orcid":true,"given":"Robert L.","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Global Medicines Development, Indivior Inc., North Chesterfield, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert J.","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."},{"name":"Centre for Human Drug Research, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0289-6432","authenticated-orcid":true,"given":"Monique","family":"van Velzen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Niesters","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3161-3945","authenticated-orcid":true,"given":"Albert","family":"Dahan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine M.","family":"Laffont","sequence":"additional","affiliation":[{"name":"Global Medicines Development, Indivior Inc., North Chesterfield, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxaa011"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/wps.20846"},{"key":"B3","unstructured":"US Centers for Disease Control and Prevention. 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