{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:37:17Z","timestamp":1779295037336,"version":"3.51.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100021069","name":"Indivior Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100021069","id-type":"DOI","asserted-by":"crossref"}]},{"name":"VCU School of Pharmacy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to improve the oral bioavailability of buprenorphine by inhibiting presystemic metabolism via the oral co-administration of \u2018Generally Recognized as Safe\u2019 compounds, thus providing an orally administered drug product with less variability and comparable or higher exposure compared with the sublingual route.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present studies were performed in Sprague Dawley rats following either intravenous or oral administration of buprenorphine\/naloxone and oral co-administration of \u2018Generally Recognized as Safe\u2019 compounds referred to as \u2018adjuvants\u2019. Plasma samples were collected up to 22 h postdosing followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS\/MS) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>The adjuvants increased Cmax (21 \u00b1 16 ng\/ml vs 75 \u00b1 33 ng\/ml; 3.6-fold) and AUC(0\u201322 h) (10.6 \u00b1 8.11 \u03bcg min\/ml vs 22.9 \u00b1 11.7 \u03bcg min\/ml; 2.2-fold) values of buprenorphine (control vs adjuvant-treated, respectively). The absolute oral bioavailability of buprenorphine doubled (from 1.24% to 2.68%) in the presence of the adjuvants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>One may suggest that the adjuvant treatment most likely inhibited the presystemic metabolic enzymes, thus decreasing the intestinal \u2018first-pass effect\u2019 on buprenorphine. Additional studies are now required to further explore the concept of inhibiting presystemic metabolism of buprenorphine by adjuvants to potentially increase the oral bioavailability of buprenorphine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jphp.12652","type":"journal-article","created":{"date-parts":[[2016,10,26]],"date-time":"2016-10-26T05:32:40Z","timestamp":1477459960000},"page":"23-31","source":"Crossref","is-referenced-by-count":5,"title":["Improving the oral bioavailability of buprenorphine: an<i>in-vivo<\/i>proof of concept"],"prefix":"10.1093","volume":"69","author":[{"given":"Anand","family":"Joshi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, VCU School of Pharmacy , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Halquist","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, VCU School of Pharmacy , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zacharoula","family":"Konsoula","sequence":"additional","affiliation":[{"name":"Global Research & Development, Indivior Inc. , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Global Research & Development, Indivior Inc. , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J P","family":"Jones","sequence":"additional","affiliation":[{"name":"Global Research & Development, Indivior Inc. , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Heidbreder","sequence":"additional","affiliation":[{"name":"Global Research & Development, Indivior Inc. , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-1018","authenticated-orcid":false,"given":"Phillip M","family":"Gerk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, VCU School of Pharmacy , Richmond, VA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2024103012564235700_jphp12652-cit-0001"},{"key":"2024103012564235700_jphp12652-cit-0002","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1476-5381.1977.tb07532.x","article-title":"Agonist and antagonist properties of buprenorphine, a new antinociceptive agent","volume":"4","author":"Cowan","year":"1977","journal-title":"Br J Pharmacol"},{"key":"2024103012564235700_jphp12652-cit-0003"},{"key":"2024103012564235700_jphp12652-cit-0004","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/10673220490905688","article-title":"Office-based buprenorphine treatment for opioid-dependent patients","volume":"6","author":"Mccance-Katz","year":"2004","journal-title":"Harv Rev Psychiatry"},{"key":"2024103012564235700_jphp12652-cit-0005","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2165\/00003088-200544070-00001","article-title":"Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence","volume":"7","author":"Elkader","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"2024103012564235700_jphp12652-cit-0006","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1080\/13556210500358441","article-title":"Opioid plasma concentrations in methadone-and buprenorphine-maintained patients","volume":"4","author":"Jagsch","year":"2005","journal-title":"Addict Biol"},{"key":"2024103012564235700_jphp12652-cit-0007","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.2042-7158.1981.tb13848.x","article-title":"The systemic bioavailability of buprenorphine by various routes of administration","volume":"8","author":"Brewster","year":"1981","journal-title":"J Pharm Pharmacol"},{"key":"2024103012564235700_jphp12652-cit-0008","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/S0090-9556(25)06808-4","article-title":"Glucuronidation in vitro and in vivo. 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