{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T15:07:46Z","timestamp":1779030466626,"version":"3.51.4"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institute of Health","award":["R01 AG072714"],"award-info":[{"award-number":["R01 AG072714"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Delta-8-tetrahydrocannabinol (\u03948THC) has been growing in popularity across the United States due to its reported therapeutic benefits, including pain relief, euphoria, relaxation, and mild psychoactive effects, especially in areas where sale of delta-9-tetrahydrocannabinol (\u03949THC) is illegal. Currently, much debate surrounds \u03948THC regarding its regulatory status and whether this compound is safe and similar in pharmacokinetics to \u03949THC. To address the latter issue, a single-dose oral (7.5\u2009mg\/kg) and intravenous (IV; 1.25\u2009mg\/kg) pharmacokinetic study was performed in male Sprague-Dawley rats. A bioanalytical method was developed and validated following the FDA M10 guidelines in rat plasma to detect \u03948THC and its metabolites, 11-hydroxy-delta-8-tetrahydrocannabinol (11OH-\u03948THC) and 11-carboxy-delta-8-tetrahydrocannabinol (11COOH-\u03948THC). This method was then applied to analyze the plasma samples collected during the preclinical pharmacokinetic studies. The plasma concentration-time profiles were subjected to non-compartmental analysis to obtain pharmacokinetic parameters. When administered intravenously, \u03948THC had a clearance of 5.6\u2009\u00b1\u20090.4\u2009L\/h\/kg, a volume of distribution of 108.4\u2009\u00b1\u20098.9\u2009L\/kg, and elimination half-life of 13.9\u2009\u00b1\u20092.0\u2009h. \u03948THC pharmacokinetic parameters following oral administration, exhibited a Cmax (peak plasma concentration) of 13.4\u2009\u00b1\u20090.9\u2009ng\/mL with a Tmax (time to reach Cmax) of 0.5\u2009\u00b1\u20090.1\u2009h, and an oral bioavailability of 3.0\u2009\u00b1\u20090.3%. The clearance of \u03948THC when dosed IV is higher than rat hepatic blood flow (4.8\u2009L\/h\/kg), indicative of extrahepatic clearance. \u03948THC also had a large volume of distribution, indicating extravascular distribution. Overall, \u03948THC had very low oral bioavailability, while the clearance and volume of distribution values indicate extensive tissue distribution with contribution of extrahepatic clearance.<\/jats:p>","DOI":"10.1093\/jat\/bkaf105","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T12:30:38Z","timestamp":1765801838000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic study of delta-8-tetrahydrocannabinol in male rats using a validated bioanalytical method"],"prefix":"10.1093","volume":"50","author":[{"given":"Alexandria S","family":"Senetra","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida , Gainesville, FL 32610,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sushobhan","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of 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College of Pharmacy, University of Florida , Gainesville, FL 32610,","place":["United States"]},{"name":"UF-Translational Drug Development Core, Clinical and Translational Science Institute, University of Florida , Gainesville, FL 32610,","place":["United States"]},{"name":"Center for Addiction Research and Education, University of Florida , Gainesville, FL 32610,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4039","authenticated-orcid":false,"given":"Abhisheak","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Florida , Gainesville, FL 32610,","place":["United States"]},{"name":"UF-Translational Drug Development Core, Clinical and Translational Science Institute, University of Florida , Gainesville, FL 32610,","place":["United 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