{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:18:06Z","timestamp":1783333086444,"version":"3.54.6"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study aimed to assess the pharmacokinetics, bioequivalence, and safety of a generic entacapone\/levodopa\/carbidopa (100\/25\/200\u00a0mg) tablet formulation compared to its reference listed drug (RLD, Stalevo) in healthy Chinese adults.\u00a0A randomized, open\u2010label, single\u2010dose, four\u2010period crossover study was conducted under fasting and fed conditions, with a 5\u2010day washout. A total of 68 subjects were enrolled and randomly assigned (1:1) to receive a single oral dose of either the test or reference formulation. Plasma concentrations of analytes were quantified using liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS), and key pharmacokinetic parameters (C\n                    <jats:sub>max<\/jats:sub>\n                    , AUC\n                    <jats:sub>0\u2013t<\/jats:sub>\n                    , AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) were calculated.\u00a0Under both fasting and fed conditions, bioequivalence was assessed under both fasting and fed conditions using the reference\u2010scaled average bioequivalence (RSABE) or average bioequivalence (ABE) approach. For the key pharmacokinetic parameters (C\n                    <jats:sub>max<\/jats:sub>\n                    , AUC\n                    <jats:sub>0\u2013t<\/jats:sub>\n                    , and AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ), the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) all fell within the 80.00%\u2013125.00% range, or the one\u2010sided 95% upper confidence bound for the scaled difference was \u22640 and the point estimate of the GMR between the test and reference formulations fell within the 80.00%\u2013125.00% range, thus confirming bioequivalence. Concomitant high\u2010fat food intake had a certain impact on the pharmacokinetics of each active ingredient. Adverse events (AEs) were mild, with no serious AEs reported, indicating comparable safety profiles.\u00a0In conclusion, the generic formulation is bioequivalent to the RLD and demonstrates an acceptable safety profile in healthy Chinese subjects.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.70071","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:44:53Z","timestamp":1780051493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Tolerability of Entacapone, Levodopa, and Carbidopa Tablets in Healthy Chinese Subjects: A Randomized, Open\u2010Label, Four\u2010Period Crossover Study Under Fasting and Fed Conditions"],"prefix":"10.1002","volume":"15","author":[{"given":"Jingyan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Health Industry Sichuan Tourism University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Health Industry Sichuan Tourism University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tao","sequence":"additional","affiliation":[{"name":"Phase I Clinical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Health Industry Sichuan Tourism University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zou","sequence":"additional","affiliation":[{"name":"College of Health Industry Sichuan Tourism University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Health Industry Sichuan Tourism University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lan","sequence":"additional","affiliation":[{"name":"Shandong Jewim Pharmaceutical Co. Ltd.  Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01478-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14108"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15992"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15994"},{"key":"e_1_2_10_6_1","first-page":"S64","article-title":"Levodopa\/carbidopa\/entacapone (Stalevo)","volume":"62","author":"Robert AH","year":"2004","journal-title":"Neurology"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde.15.96"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0184-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22343"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e31825645d1"},{"key":"e_1_2_10_11_1","first-page":"155","article-title":"The impact of COMT\u2010inhibition on gastrointestinal levodopa absorption in patients with Parkinson's disease","volume":"2","author":"Thomas M","year":"2010","journal-title":"Clin Med Insights Ther"},{"issue":"2","key":"e_1_2_10_12_1","first-page":"253","article-title":"Pharmacokinetics of levodopa","volume":"257","author":"Manuela C","year":"2010","journal-title":"J Neurol"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02180.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.52.9.1063"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.4.4.589"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.70071","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.70071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:54:34Z","timestamp":1783331674000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.70071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":14,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/cpdd.70071"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.70071","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2026-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70071"}}