{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:18:26Z","timestamp":1755796706861,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["UG3 DA048338"],"award-info":[{"award-number":["UG3 DA048338"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The aim of this study is to determine if extended\u2010release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release\u2010controlling polymers, poly\u2010D\u2010L\u2010lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5\u2009months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4\u2009micrograms (mcg) \u2010 (10\u2009mcg\/kg\/dose), while the NTX implanted animals received a dose of 8\u2009mcg (20\u2009mcg\/kg\/dose). The <jats:italic>minimum active dose of fentanyl<\/jats:italic> that caused <jats:italic>a<\/jats:italic>\u2009&gt;\u200950\u2009\u00b1\u20092% depression in the respiration rate in the placebo implanted rodents was 4\u2009mcg. The respiration rate of the placebo implanted rats dropped from 208\u2009\u00b1\u200914 breaths\/minute at predose, to 84\u2009\u00b1\u200912 breaths\/minute (<jats:italic>p<\/jats:italic>\u2009=\u20090.0003) at 2\u2009min. In contrast, all NTX implanted animals easily tolerated <jats:italic>twice<\/jats:italic> the dose of 8\u2009mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate\u2009=\u2009increased from 164\u2009\u00b1\u200922 breaths\/minute at predose to 178\u2009\u00b1\u200917 breaths\/minute (<jats:italic>p<\/jats:italic>\u2009=\u20090.24) at 2\u2009min. The mean plasma concentrations of NTX, 3.5\u2009months after implantation, ranged from 7.4 (\u00b11.1) ng\/mL to 80.3 (\u00b137.5) ng\/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl\u2010induced respiratory depression in rodents as compared with placebo implants, 3.5\u2009months after implantation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/adb.13350","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T16:09:51Z","timestamp":1698422991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fentanyl\u2010induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5\u2009months"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0350-2204","authenticated-orcid":false,"given":"Jeffrey D.","family":"Benner","sequence":"first","affiliation":[{"name":"The Drug Delivery Company, LLC dba Akyso, Salisbury, MD (JDB and SMC), LabCorp Drug Development Greenfield, IN (JAH), The Department of Psychiatry Johns Hopkins School of Medicine and Maryland Treatment Centers  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6633-8173","authenticated-orcid":false,"given":"Steven M.","family":"Cohen","sequence":"additional","affiliation":[{"name":"The Drug Delivery Company, LLC dba Akyso, Salisbury, MD (JDB and SMC), LabCorp Drug Development Greenfield, IN (JAH), The Department of Psychiatry Johns Hopkins School of Medicine and Maryland Treatment Centers  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Hollenbaugh","sequence":"additional","affiliation":[{"name":"The Drug Delivery Company, LLC dba Akyso, Salisbury, MD (JDB and SMC), LabCorp Drug Development Greenfield, IN (JAH), The Department of Psychiatry Johns Hopkins School of Medicine and Maryland Treatment Centers  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Fishman","sequence":"additional","affiliation":[{"name":"The Drug Delivery Company, LLC dba Akyso, Salisbury, MD (JDB and SMC), LabCorp Drug Development Greenfield, IN (JAH), The Department of Psychiatry Johns Hopkins School of Medicine and Maryland Treatment Centers  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint14010004"},{"volume-title":"Drug Overdose Death Rates","year":"2023","author":"NIDA","key":"e_1_2_10_3_1"},{"volume-title":"Opioid Overdose","year":"2022","author":"Schiller EY","key":"e_1_2_10_4_1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6911a4"},{"volume-title":"Fentanyl Drug 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