{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:54:26Z","timestamp":1783090466499,"version":"3.54.6"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"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":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Ecopipam is a dopamine\u20101 (D1) receptor antagonist in development for Tourette syndrome. In\u00a0vitro data showed that ecopipam is metabolized to ecopipam glucuronide through uridine diphosphate\u2010glucuronosyltransferase 1A9 and to EBS\u2010101\u201040853 (previously called N\u2010desmethylecopipam or SCH 40853) through cytochrome P450 3A4. This open\u2010label, non\u2010randomized, mass balance study investigated metabolism and elimination pathways of ecopipam. A single oral dose of ecopipam 179.2\u2009mg containing 88.5\u2009\u03bcCi (3.27\u2009MBq) of [\n 14<\/jats:sup>\n C]\u2010labeled ecopipam was administered to 8 healthy males. Total radioactivity, ecopipam, and ecopipam metabolite concentrations were measured in blood, plasma, urine, and feces periodically until discharge (between Days 8 and 15 postdose). Pooled plasma was used to identify and quantify unknown metabolites. Overall, 83.3% of radioactivity was recovered in urine as metabolites (<\u20091% as ecopipam), and 8.27% was excreted in feces (6.43% as ecopipam). Ecopipam glucuronide accounted for 80.0% of radioactivity in plasma and 66.9% of radioactivity in urine. EBS\u2010101\u201040853 accounted for 10.5% of the plasma AUC\n \u221e<\/jats:sub>\n for ecopipam. Geometric mean half\u2010lives of ecopipam, EBS\u2010101\u201040853, and total radioactivity in plasma were 17.3, 25.6, and 94.1\u2009h, respectively. Uncharacterized metabolites P3 and P5, \u2018corrected\u2019 for extraction efficiency, had plasma half\u2010lives (97.4 and 122\u2009h, respectively) similar to total radioactivity. Unknown P3, P4, and P5 metabolites accounted for 4.62%, 0.243%, and 6.03%, respectively, of plasma radioactivity. Ecopipam is primarily metabolized to ecopipam glucuronide, with only 10.5% metabolized to EBS\u2010101\u201040853. The long half\u2010life of plasma radioactivity was attributed to previously uncharacterized metabolites that each accounted for <\u200910% of radioactivity and were considered not clinically relevant.\n <\/jats:p>","DOI":"10.1111\/cts.70587","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T03:29:22Z","timestamp":1779074962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ecopipam, a Dopamine\n D1<\/scp>\n Receptor Antagonist: Pharmacokinetics, Mass Balance, and Metabolism in Healthy Volunteers"],"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"English","sequence":"additional","affiliation":[{"name":"Pharmaron Germantown Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Dymond","sequence":"additional","affiliation":[{"name":"Labcorp Leeds\/Harrogate UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Labcorp Leeds\/Harrogate UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Stow","sequence":"additional","affiliation":[{"name":"Labcorp Leeds\/Harrogate UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Labcorp Leeds\/Harrogate UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Schleyer","sequence":"additional","affiliation":[{"name":"Emalex Biosciences, Inc. Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Wanaski","sequence":"additional","affiliation":[{"name":"Paragon Biosciences, LLC Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3233\/BEN-120296"},{"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":"10.1212\/WNL.0000000000007466"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-021-01899-z"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12466"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13403"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70495"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.56"},{"key":"e_1_2_10_12_1","volume-title":"Shargel and Yu's Applied Biopharmaceutics and Pharmacokinetics, 8th Edition","author":"Ducharme M. 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