{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:24:43Z","timestamp":1788459883500,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>In response to increased illicit use of synthetic opioids, various \u03bc\u2010receptor antagonist formulations, with varied pharmacological characteristics, have been and are being developed. To understand how pharmacologic characteristics such as absorption rate and clearance rate affect reversal in treating community opioid overdose, we used our previously published translational opioid model. We adapted this model with <jats:italic>in vitro<\/jats:italic> receptor binding data and clinical pharmacokinetic data of three intranasal nalmefene formulations along with an intranasal naloxone formulation to study the reversal of fentanyl and carfentanil\u2010induced respiratory depression in chronic opioid users. Nalmefene has a longer plasma half\u2010life and slower unbinding from the \u03bc\u2010receptor compared to naloxone. For a more rapid reversal of acute overdose\u2010induced respiratory depression, a fast\u2010absorbing antagonist formulation may be of greater utility than a slow\u2010absorbing one containing the same dosage of the antagonist. For preventing renarcotization caused by a long opioid exposure, a slow\u2010clearing antagonist with slow unbinding from the receptor may be of value. While a more potent antagonist with a longer half\u2010life may have the potential to facilitate recovery from respiratory depression for overdose with synthetic opioids, such interventions may also lead to longer and more pronounced withdrawal. This emphasizes the need for a nuanced consideration of several facets while choosing a \u03bc\u2010receptor antagonist, dose, and formulation to treat community opioid overdose cases.<\/jats:p>","DOI":"10.1002\/cpt.3527","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T05:29:56Z","timestamp":1738128596000},"page":"836-845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Toward Developing Alternative Opioid Antagonists for Treating Community Overdose: A Model\u2010Based Evaluation of Important Pharmacological Attributes"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-5820","authenticated-orcid":false,"given":"Anik","family":"Chaturbedi","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research Food &amp; 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