{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T04:27:29Z","timestamp":1770956849221,"version":"3.50.1"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T00:00:00Z","timestamp":1616284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013223","name":"PTC Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013223","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>6\u03b2\u2010Hydroxy\u201021\u2010desacetyl deflazacort (6\u03b2\u2010OH\u201021\u2010desDFZ) is a major circulating but not biologically active metabolite of deflazacort (DFZ). In vitro studies were performed to evaluate cytochrome P450 (CYP)\u2010 and transporter\u2010mediated drug interaction potentials of 6\u03b2\u2010OH\u201021\u2010desDFZ. Up to 50\u00a0\u00b5M, the highest soluble concentration in the test system, 6\u03b2\u2010OH\u201021\u2010desDFZ weakly inhibited (IC<jats:sub>50<\/jats:sub>\u00a0&gt;\u00a050\u00a0\u00b5M) the enzyme activity of CYPs 1A2, 2B6, 2C8, 2C9, and 2D6, while moderately inhibiting CYP2C19 and CYP3A4 with IC<jats:sub>50<\/jats:sub> values of approximately 50 and 35\u00a0\u03bcM, respectively. The inhibition was neither time\u2010dependent nor metabolism\u2010based. Incubation of up to 50\u00a0\u00b5M 6\u03b2\u2010OH\u201021\u2010desDFZ with plated cryopreserved human hepatocytes for 48\u00a0h resulted in no meaningful concentration\u2010dependent induction of either mRNA levels or enzyme activity of CYP1A2, CYP2B6, or CYP3A4. In transporter inhibition assays, 6\u03b2\u2010OH\u201021\u2010desDFZ, up to 50\u00a0\u00b5M, did not show interaction with human OAT1, OAT3, and OCT2 transporters. It weakly inhibited (IC<jats:sub>50<\/jats:sub>\u00a0&gt;\u00a050\u00a0\u00b5M) human MATE1, MATE2\u2010K, and OCT1 transporter activity, and moderately inhibited human MDR1, OATP1B1, and OATP1B3 transporter activity with IC<jats:sub>50<\/jats:sub> values of 19.81\u00a0\u03bcM, 37.62\u00a0\u03bcM, and 42.22\u00a0\u03bcM, respectively. <jats:sup>14<\/jats:sup>C\u20106\u03b2\u2010OH\u201021\u2010desDFZ was biosynthesized using bacterial biotransformation and the subsequent study showed that 6\u03b2\u2010OH\u201021\u2010desDFZ was not a substrate for human BCRP, MDR1, MATE1, MATE2\u2010K, OAT1, OATP1B1, OATP1B3, and OCT2 transporters, but appeared to be an in vitro substrate for the human OAT3 uptake transporter. At plasma concentrations of 6\u03b2\u2010OH\u201021\u2010desDFZ seen in the clinic, CYP\u2010 and transporter\u2010mediated drug\u2013drug interactions are not expected following administration of a therapeutic dose of DFZ in Duchenne muscular dystrophy (DMD) patients.<\/jats:p>","DOI":"10.1002\/prp2.748","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T02:09:27Z","timestamp":1616378967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In vitro cytochrome P450\u2010 and transporter\u2010mediated drug interaction potential of 6\u03b2\u2010hydroxy\u201021\u2010desacetyl deflazacort\u2014A major human metabolite of deflazacort"],"prefix":"10.1002","volume":"9","author":[{"given":"Jiyuan","family":"Ma","sequence":"first","affiliation":[{"name":"PTC Therapeutics Inc. South Plainfield NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Beers","sequence":"additional","affiliation":[{"name":"PTC Therapeutics Inc. South Plainfield NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Manohar","sequence":"additional","affiliation":[{"name":"Hypha Discovery Ltd Abingdon Oxfordshire UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Roe","sequence":"additional","affiliation":[{"name":"Selcia Ltd Ongar Essex UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Colacino","sequence":"additional","affiliation":[{"name":"PTC Therapeutics Inc. South Plainfield NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4692-7499","authenticated-orcid":false,"given":"Ronald","family":"Kong","sequence":"additional","affiliation":[{"name":"PTC Therapeutics Inc. South Plainfield NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S110163"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(91)90039-U"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2044"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26736"},{"key":"e_1_2_11_6_1","unstructured":"Emflaza [deflazacort] Prescribing Information.https:\/\/www.emflaza.com\/wp\u2010content\/themes\/emflaza\u2010patient\/pdf\/Prescribing\u2010Information.pdf. Accessed June 2019."},{"key":"e_1_2_11_7_1","first-page":"335","article-title":"Metabolism of deflazacort in the rat, dog and man","volume":"7","author":"Martinelli E","year":"1979","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_11_8_1","first-page":"9","article-title":"Pharmacokinetics and metabolism of deflazacort in the rat, dog, monkey and man","volume":"171","author":"Assandri A","year":"1984","journal-title":"Adv Exp Med Biol"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.677"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx2005212"},{"key":"e_1_2_11_11_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.Guidance for industry: in vitro drug interaction studies \u2014 cytochrome P450 enzyme\u2010 and transporter\u2010mediated drug interactions.2020.https:\/\/www.fda.gov\/media\/134582\/download"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2018.1512018"},{"key":"e_1_2_11_13_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.Guidance for Industry: In Vitro Metabolism\u2010 and Transporter\u2010 Mediated Drug\u2010Drug Interaction Studies.2017.https:\/\/www.fda.gov\/media\/108130\/download"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4598(200009)23:9<1344::AID-MUS4>3.0.CO;2-F"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003217"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.748","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.748","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.748","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T04:29:09Z","timestamp":1693283349000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,21]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/prp2.748"],"URL":"https:\/\/doi.org\/10.1002\/prp2.748","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,21]]},"assertion":[{"value":"2021-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00748"}}