{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:03:26Z","timestamp":1790996606600,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inhibiting catechol\u2010O\u2010methyltransferase extends the plasma half\u2010life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the effects of once\u2010daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 24 patients with PD and motor fluctuations were enrolled in an exploratory, open\u2010label, modified cross\u2010over trial. Participants first received levodopa\/carbidopa 500\/125\u2009mg (five intakes) for 2\u2009weeks and were then randomly assigned (1:1) to levodopa\/carbidopa 400\/100\u2009mg given over either four or five daily intakes plus opicapone 50\u2009mg for an additional 2\u2009weeks. Levodopa 12\u2010hour pharmacokinetics was the primary outcome (ie, excluding the effect of last\/evening levodopa\/carbidopa intake), with motor complications evaluated as secondary outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over 12\u2010hour pharmacokinetics and compared with five\u2010intake levodopa\/carbidopa 500\/125\u2009mg without opicapone, maximal levodopa concentrations were similar or nonsignificantly higher on both levodopa\/carbidopa 400\/100\u2009mg regimens plus opicapone. Despite a 100\u2009mg lower total levodopa\/carbidopa daily dose, adding opicapone 50\u2009mg at least doubled the levodopa plasma half\u2010life and minimal concentrations, with a significant \u224830% increase in total exposure. The levodopa fluctuation index was only significantly lower for the five intakes plus opicapone regimen (difference of \u221271.8%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.0001). Modifications to levodopa pharmacokinetics were associated with decreased <jats:italic>off<\/jats:italic> time and increased <jats:italic>on<\/jats:italic> time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combining opicapone 50\u2009mg with a 100\u2009mg lower daily dose of levodopa provides higher levodopa bioavailability with avoidance of trough levels. Despite the lower levodopa dose, modifying the levodopa pharmacokinetic profile with opicapone was associated with decreased <jats:italic>off<\/jats:italic> time and increased <jats:italic>on<\/jats:italic> time. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29193","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T03:58:51Z","timestamp":1661918331000},"page":"2272-2283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-5113","authenticated-orcid":false,"given":"Joaquim J.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina Universidade de Lisboa  Lisbon Portugal"},{"name":"CNS\u2010Campus Neurol\u00f3gico S\u00e9nior  Torres Vedras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Poewe","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-6397","authenticated-orcid":false,"given":"Olivier","family":"Rascol","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Clinical Pharmacology University of Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Stocchi","sequence":"additional","affiliation":[{"name":"Department of Neurology University San Raffaele and IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) San Raffaele Pisana  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-2807","authenticated-orcid":false,"given":"Angelo","family":"Antonini","sequence":"additional","affiliation":[{"name":"Parkinson and Movement Disorders Unit, Study Center for Neurodegeneration Department of Neurosciences University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Moreira","sequence":"additional","affiliation":[{"name":"BIAL\u2013Portela &amp; C<sup>a<\/sup> S.A, Research &amp; Development Department  Coronado Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"BIAL\u2013Portela &amp; C<sup>a<\/sup> S.A, Research &amp; Development Department  Coronado Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-4850","authenticated-orcid":false,"given":"Jos\u00e9\u2010Francisco","family":"Rocha","sequence":"additional","affiliation":[{"name":"BIAL\u2013Portela &amp; C<sup>a<\/sup> S.A, Research &amp; Development Department  Coronado Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcio","family":"Soares\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"BIAL\u2013Portela &amp; C<sup>a<\/sup> S.A, Research &amp; Development Department  Coronado Portugal"},{"name":"University of Porto, Pharmacology Department  Porto Portugal"},{"name":"MedInUP\u2013Center for Drug Discovery and Innovative Medicines University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27690"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012868"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2019.12.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23875"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm1001524"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-012-0024-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2003.034553"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.38.3.419"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2021.1968298"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241040-00003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26078"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70521-X"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S1660"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.7.10.1399"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12666"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1701-2"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00336-1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.4703"},{"key":"e_1_2_10_20_1","article-title":"Pharmacokinetics of Opicapone and effect on COMT and levodopa pharmacokinetics in patients with Parkinson's disease","volume":"34","author":"Loewen G Lewitt P","year":"2019","journal-title":"Mov Disord"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.3.181"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20248"},{"key":"e_1_2_10_23_1","first-page":"218","volume-title":"Clinical global impressions. 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