{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:40:46Z","timestamp":1791906046778,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Most stimulants used to treat attention\u2010deficit\/hyperactivity disorder are administered in the morning and absorbed in the upper gastrointestinal tract. DR\/ER\u2010MPH (formerly HLD200), an evening\u2010dosed delayed\u2010release and extended\u2010release methylphenidate, is predicted to be absorbed in the proximal colon. The pharmacokinetic (PK) profile of DR\/ER\u2010MPH is characterized by an 8\u2010 to 10\u2010hour delay in initial methylphenidate absorption and a subsequent gradual increase in plasma concentration, followed by a slow decline. To examine the relationship of absorption site to pharmacokinetics, the DR\/ER\u2010MPH formulation was altered to release methylphenidate in the small intestine and distal colon. The 3 formulations were administered in an open\u2010label, 3\u2010way, crossover study in healthy adults (N = 18). Compared with the small intestine formulation, the PK profile of the proximal colon (DR\/ER\u2010MPH) formulation exhibited a longer delay before initial methylphenidate absorption, decreased peak methylphenidate concentration, increased time to peak concentration, and decreased bioavailability; these characteristics were amplified in the distal colon formulation. Safety profiles fell within the expectations for methylphenidate products. Modeled PK profiles were similar between the small intestine formulation and a morning\u2010dosed extended\u2010release methylphenidate (both predicted to release methylphenidate in the upper gastrointestinal tract), providing additional evidence that the PK profile of DR\/ER\u2010MPH is shaped by colonic absorption.<\/jats:p>","DOI":"10.1002\/cpdd.1089","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T09:49:27Z","timestamp":1647942567000},"page":"966-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of Colonic Absorption on the Pharmacokinetic Properties of Delayed\u2010Release and Extended\u2010Release Methylphenidate: In Vivo, In Vitro, and Modeling Evaluations"],"prefix":"10.1002","volume":"11","author":[{"given":"Bev","family":"Incledon","sequence":"first","affiliation":[{"name":"Ironshore Pharmaceuticals &amp; Development, Inc.  Camana Bay Grand Cayman Cayman Islands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Incledon","sequence":"additional","affiliation":[{"name":"Ironshore Pharmaceuticals &amp; Development, Inc.  Camana Bay Grand Cayman Cayman Islands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gomeni","sequence":"additional","affiliation":[{"name":"PharmacoMetrica France  La Fouillade France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra L.","family":"Uchida","sequence":"additional","affiliation":[{"name":"Highland Therapeutics Inc.  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