{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:09:40Z","timestamp":1791727780999,"version":"4.3.4"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T00:00:00Z","timestamp":1651276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BIAL"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa\/dopa decarboxylase inhibitor formulations through an increase in levodopa plasma bioavailability. Catechol-O-methyltransferase inhibitors influence the homocysteine metabolism associated with levodopa\/dopa decarboxylase application. The objectives of this study were to compare the impact of additional single-day entacapone or opicapone intake on the pharmacokinetic plasma behaviour of levodopa, 3-O-methyldopa and total homocysteine in 15 Parkinson\u2019s disease patients, with concomitant scoring of motor symptoms, under standardized conditions. The patients received opicapone plus two doses of 100 mg levodopa\/carbidopa and, one week later, two doses of levodopa\/carbidopa\/entacapone or vice versa. Levodopa, 3-O-methyldopa and total homocysteine were determined with reversed-phase high-performance liquid chromatography. Levodopa bioavailability and its maximum concentration were higher with opicapone. The computed peak-to-trough difference was lower after the second levodopa administration with entacapone. The fluctuation index of levodopa did not differ between both conditions. 3-O-methyldopa decreased on both days. Homocysteine levels did not significantly vary between both conditions. A significant homocysteine decrease occurred with entacapone, but not with opicapone. Motor behaviour improved with entacapone, but not with opicapone. Opicapone baseline scores were significantly better, and thus the potential for the improvement in motor symptoms was lower compared with the entacapone condition. The higher levodopa bioavailability with opicapone suggests that it is more efficacious than entacapone for the amelioration of \u201coff\u201d phenomena in fluctuating patients when co-administered with a levodopa\/dopa decarboxylase inhibitor regimen. Both compounds prevented an increase in homocysteine, which is a metabolic marker for an impaired capacity in the performance of methylation processes.<\/jats:p>","DOI":"10.3390\/cells11091511","type":"journal-article","created":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T06:23:08Z","timestamp":1651386188000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effects of One-Day Application of Levodopa\/Carbidopa\/Entacapone versus Levodopa\/Carbidopa\/Opicapone in Parkinson\u2019s Disease Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-0753","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany"},{"name":"Faculty of Medicine, Ruhr University of Bochum, Universit\u00e4tsstra\u00dfe 150, 44801 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Schlegel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kreisklinikum Siegen, Weidenauer Str. 76, 57076 Siegen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Zingler","sequence":"additional","affiliation":[{"name":"Swiss Pharm Audit GmbH, R\u00f6sliweg 11, 8404 Winterthur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Michael","family":"Thiede","sequence":"additional","affiliation":[{"name":"Thanares GmbH, Hermannswerder 14, 14473 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1056\/NEJMoa033447","article-title":"Levodopa and the progression of Parkinson\u2019s disease","volume":"351","author":"Fahn","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s40265-014-0343-0","article-title":"Catechol-O-methyltransferase inhibitors in Parkinson\u2019s disease","volume":"75","year":"2015","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000117399","article-title":"Comparison of immediate-release and controlled release carbidopa\/levodopa in Parkinson\u2019s disease. A multicenter 5-year study. The CR First Study Group","volume":"37","author":"Block","year":"1997","journal-title":"Eur. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1136\/jnnp.74.8.1071","article-title":"Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson\u2019s disease: A randomised, placebo controlled, double blind, six month study","volume":"74","author":"Brooks","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/ene.13914","article-title":"Long-term efficacy of opicapone in fluctuating Parkinson\u2019s disease patients: A pooled analysis of data from two phase 3 clinical trials and their open-label extensions","volume":"26","author":"Ferreira","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_6","first-page":"S81","article-title":"Pharmacokinetics, pharmacodynmics and tolerability of opicapone, a novel COMT inhibitor, during multiple dose rise regimen in healthy male subjects","volume":"18S2","author":"Rocha","year":"2012","journal-title":"Parkinsonism. Relat. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00228-014-1701-2","article-title":"Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations","volume":"70","author":"Rocha","year":"2014","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s40262-012-0024-7","article-title":"Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: Prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor","volume":"52","author":"Almeida","year":"2013","journal-title":"Clin. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00228-009-0622-y","article-title":"Comparison of pharmacokinetic profile of levodopa throughout the day between levodopa\/carbidopa\/entacapone and levodopa\/carbidopa when administered four or five times daily","volume":"65","author":"Korpela","year":"2009","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/mds.20717","article-title":"Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels","volume":"21","author":"Erdmann","year":"2006","journal-title":"Mov. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/ana.410210610","article-title":"3-O-methyldopa and the response to levodopa in Parkinson\u2019s disease","volume":"21","author":"Nutt","year":"1987","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s00702-009-0275-0","article-title":"Peripheral COMT inhibition prevents levodopa associated homocysteine increase","volume":"116","author":"Muhlack","year":"2009","journal-title":"J. Neural. Transm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/mds.22607","article-title":"Homocysteine levels after acute levodopa intake in patients with Parkinson\u2019s disease","volume":"24","author":"Kuhn","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.parkreldis.2010.07.012","article-title":"Acute homocysteine rise after repeated levodopa application in patients with Parkinson\u2019s disease","volume":"16","author":"Muhlack","year":"2010","journal-title":"Parkinsonism. Relat. Disord."},{"key":"ref_15","first-page":"153","article-title":"Unified Parkinson\u2019s Disease Rating Scale","volume":"Volume 2","author":"Fahn","year":"1987","journal-title":"Recent Developments in Parkinson\u2019s Disease"},{"key":"ref_16","first-page":"S7","article-title":"Pharmacokinetics of opicapone and effect on COMT and levodopa pharmacokinetics in patients with Parkinson\u2019s disease. Parkinsonism & Related Disorders","volume":"34","author":"Loewen","year":"2019","journal-title":"J. Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s00702-006-0442-5","article-title":"Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa\/carbidopa with and without entacapone in patients with Parkinson\u2019s disease","volume":"113","author":"Erdmann","year":"2006","journal-title":"J. Neural. Transm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00702-019-02057-1","article-title":"Bound, free, and total L-dopa measurement in plasma of Parkinson\u2019s disease patients","volume":"126","author":"Thiede","year":"2019","journal-title":"J. Neural. Transm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1136\/jnnp.60.1.36","article-title":"Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations","volume":"60","author":"Ruottinen","year":"1996","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/mds.22343","article-title":"Double-blind trial of levodopa\/carbidopa\/entacapone versus levodopa\/carbidopa in early Parkinson\u2019s disease","volume":"24","author":"Hauser","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ana.22060","article-title":"Initiating levodopa\/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE-PD study","volume":"68","author":"Stocchi","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00210-011-0629-7","article-title":"Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson\u2019s disease","volume":"383","author":"Woitalla","year":"2011","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1568-1637(03)00013-8","article-title":"Methylation and acetylation in nervous system development and neurodegenerative disorders","volume":"2","author":"Mattson","year":"2003","journal-title":"Ageing Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/mdc3.12921","article-title":"Levodopa Equivalent Dose Conversion Factors: An Updated Proposal Including Opicapone and Safinamide","volume":"7","author":"Schade","year":"2020","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/mds.26560","article-title":"Hypomethylation in Parkinson\u2019s disease: An epigenetic drug effect?","volume":"31","author":"Kohlhepp","year":"2016","journal-title":"Mov. 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