{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:28:30Z","timestamp":1791851310999,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deutetrabenazine (Austedo, Teva), an approved treatment of chorea in Huntington's disease and tardive dyskinesia in adult patients, is a rationally designed deuterated form of tetrabenazine. Two studies assessed the pharmacokinetics and safety of deutetrabenazine compared with tetrabenazine, and the effects of food on absorption of the deuterated active metabolites, \u03b1\u2010dihydrotetrabenazine (\u03b1\u2010HTBZ) and \u03b2\u2010dihydrotetrabenazine (\u03b2\u2010HTBZ). One study was an open\u2010label 2\u2010part study in healthy volunteers; the first part included a crossover single dose of two 15 mg candidate deutetrabenazine formulations in fed and fasted states compared with tetrabenazine 25 mg in the fasted state, and the second part included single and repeated dosing of the commercial formulation of deutetrabenazine (7.5, 15, and 22.5 mg) compared with tetrabenazine 25 mg. The second study was an open\u2010label 5\u2010way crossover study in healthy volunteers (n = 32) to evaluate relative bioavailability of 4 dose levels of the commercial formulation of deutetrabenazine (6, 12, 18, and 24 mg) with a standard meal and 18 mg with a high\u2010fat meal. Both studies confirmed longer half\u2010lives for active metabolites and lower peak\u2010to\u2010trough fluctuations for the sum of the metabolites (total [\u03b1+\u03b2]\u2010HTBZ) following deutetrabenazine compared with tetrabenazine (3\u2010 to 4\u2010fold and 11\u2010fold, respectively) in steady\u2010state conditions. Deutetrabenazine doses estimated to provide total (\u03b1+\u03b2)\u2010HTBZ exposure comparable to tetrabenazine 25 mg were 11.4\u201013.2 mg. Food had no effect on exposure to total (\u03b1+\u03b2)\u2010HTBZ, as measured by AUC. Although the total (\u03b1+\u03b2)\u2010HTBZ C<jats:sub>max<\/jats:sub> of deutetrabenazine was increased by \u224850% in the presence of food, it remained lower than that of tetrabenazine.<\/jats:p>","DOI":"10.1002\/cpdd.882","type":"journal-article","created":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T17:35:09Z","timestamp":1602351309000},"page":"647-659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Pharmacokinetics of Deutetrabenazine and Tetrabenazine: Dose Proportionality and Food Effect"],"prefix":"10.1002","volume":"10","author":[{"given":"Frank","family":"Schneider","sequence":"first","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd Ratiopharm GmbH  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stamler","sequence":"additional","affiliation":[{"name":"Formerly of Teva Pharmaceutical Industries Ltd currently Alterity Therapeutics Limited  Newark California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Bradbury","sequence":"additional","affiliation":[{"name":"Formerly of Teva Pharmaceutical Industries Ltd currently Alterity Therapeutics Limited  Newark California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pippa S.","family":"Loupe","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd  West Chester Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Hellriegel","sequence":"additional","affiliation":[{"name":"Formerly of Teva Pharmaceuticals Ltd currently Aclaris Therapeutics Inc.  Wayne Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna S.","family":"Cox","sequence":"additional","affiliation":[{"name":"Formerly of Teva Pharmaceuticals Ltd currently Pfizer Corporation  Norristown Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha\u2010Matti","family":"Savola","sequence":"additional","affiliation":[{"name":"Teva Pharmaceuticals International GmbH  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Forrest","family":"Gordon","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd  West Chester Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rabinovich\u2010Guilatt","sequence":"additional","affiliation":[{"name":"Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.8655"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2018.1403899"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003960"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(17)30236-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2019.1674281"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000198586.85250.13"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318263c443"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028018797110"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2014.943184"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.02.046"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0874-x"},{"issue":"12","key":"e_1_2_8_13_1","first-page":"690","article-title":"Tetrabenazine (Xenazine), an FDA\u2010approved treatment option for Huntington's disease\u2013related chorea","volume":"33","author":"Yero T","year":"2008","journal-title":"Pharm. Ther."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12754"},{"key":"e_1_2_8_15_1","unstructured":"US Food and Drug Administration Guidance Document. Food\u2010Effect Bioavailability and Fed Bioequivalence Studies. Guidance for Industry.2002.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/food-effect-bioavailability-and-fed-bioequivalence-studies. Accessed June 10 2020."},{"issue":"2","key":"e_1_2_8_16_1","first-page":"250","article-title":"Pharmacokinetics of tetrabenazine and its major metabolite in man and rat","volume":"15","author":"Mehvar R","year":"1987","journal-title":"Drug Metab Dispos."}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.882","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.882","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T19:17:48Z","timestamp":1693423068000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,10]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/cpdd.882"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.882","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,10]]},"assertion":[{"value":"2020-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}