{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:58:06Z","timestamp":1779109086280,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ecopipam, a selective dopamine D1 receptor antagonist in development for Tourette syndrome, is primarily converted by uridine diphosphate\u2010glucuronosyltransferase (UGT)1A9 to ecopipam glucuronide, with a minor metabolic pathway by cytochrome P450 3A4 forming EBS\u2010101\u201040853 (also referred to as N\u2010desmethylecopipam or SCH 40853; also glucuronidated by UGT1A9). This open\u2010label, fixed\u2010sequence study evaluated the effect of mefenamic acid (UGT1A9 inhibitor) and divalproex sodium extended release (ER; general UGT inhibitor) on the pharmacokinetics (PK) of ecopipam and its metabolites. Ecopipam 179.2\u2009mg was administered on Day 1. Cohort A received mefenamic acid 250\u2009mg every 6\u2009h from Days 7 to 13, with ecopipam 179.2\u2009mg co\u2010administered on Day 7. Cohort B received divalproex sodium ER 1250\u2009mg once daily from Days 7 to 16, with ecopipam 179.2\u2009mg co\u2010administered on Day 10. A total of 38 healthy individuals (mean [SD] age, 38.2 [8.3] years; 81.6% male) had \u2265\u20091 post\u2010dose safety or PK assessment, and 31 completed the study. Ecopipam alone or with UGT inhibitors was well tolerated. Mefenamic acid increased the\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of ecopipam (21%) and EBS\u2010101\u201040853 (12%) and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    of ecopipam (45%) and EBS\u2010101\u201040853 (42%), but did not substantially alter the PK of ecopipam glucuronide or EBS\u2010101\u201040853 glucuronide. Divalproex sodium ER increased the\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (66%) and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    (2.1\u00d7) of ecopipam, increased the\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (40%) and AUC\n                    <jats:sub>inf<\/jats:sub>\n                    (86%) of EBS\u2010101\u201040853, and decreased the\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of ecopipam glucuronide and EBS\u2010101\u201040853 glucuronide (23% and 32%, respectively). Inhibition of ecopipam metabolism indicated that ecopipam dose adjustments may be needed when administered with UGT inhibitors.\n                  <\/jats:p>","DOI":"10.1111\/cts.70495","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T07:20:49Z","timestamp":1771226449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effect of Uridine Diphosphate\u2010Glucuronosyltransferase Inhibition on the Pharmacokinetics of Ecopipam and Its Metabolites"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-2384","authenticated-orcid":false,"given":"Virginia D.","family":"Schmith","sequence":"first","affiliation":[{"name":"Schmith PK\/PD Consulting, LLC and Syntegrity Quantitative Clinical Pharmacology Collaborative  Cocoa Beach Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Graden","sequence":"additional","affiliation":[{"name":"Allucent  Cary North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Schleyer","sequence":"additional","affiliation":[{"name":"Emalex Biosciences, Inc.  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Wanaski","sequence":"additional","affiliation":[{"name":"Paragon Biosciences, LLC  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-016-0823-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00303-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022-059574"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.70091"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-021-01899-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.043117"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.017251"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.01.030"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.4.413"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1933"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.6.587"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2015.1004205"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jadr.2022.100426"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-020-02964-z"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-005-0940-7"},{"key":"e_1_2_10_17_1","first-page":"84","article-title":"P119 \u2013 Effect of Fifteen CYP3A4 In\u00a0Vitro Inducers on the Induction of CYP2B6, CYP2C8, CYP2C9, CYP2C19 and CYP3A5 in Plated Human Hepatocytes: A Trend Analysis","volume":"48","author":"Zhang J. G.","year":"2015","journal-title":"Drug Metabolism Reviews"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12024"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00895-x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250902745082"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.009340"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00075"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13010134"},{"key":"e_1_2_10_24_1","article-title":"PII\u2010123 \u2013 Metabolic Profiling of Ecopipam","volume":"115","author":"Schmith V. 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