{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:01:05Z","timestamp":1791302465766,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,1,28]],"date-time":"2011-01-28T00:00:00Z","timestamp":1296172800000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In Parkinson disease (PD), the selective C\u2010O\u2010methyltransferase (COMT) inhibitor entacapone prolongs the effect of levodopa on motor symptoms (ON time) by increasing its bioavailability. The COMT Val158Met polymorphism is equally distributed in PD patients and modulates COMT activity, which can be high (Val\/Val, <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup>), intermediate (Val\/Met, <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HL<\/jats:italic><\/jats:sup>), or low (Met\/Met, <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup>). The objective of this study was to determine the response to entacapone in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> and <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup> PD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010three PD patients, homozygous for the <jats:italic>COMT<\/jats:italic> alleles <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> (n = 17) and <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup> (n = 16), were randomized in a double\u2010blind crossover trial consisting of 2 successive acute levodopa challenges associated with 200mg entacapone or placebo. The primary endpoint was the gain in the best ON time. Secondary endpoints were levodopa pharmacokinetics and COMT activity in red blood cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The gain in the best ON time was higher in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> than in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup> patients (39 \u00b1 10 vs 9 \u00b1 9 minutes, <jats:italic>p<\/jats:italic> = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> than in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup> patients (+62 \u00b1 6% vs +34 \u00b1 8%, <jats:italic>p<\/jats:italic> = 0.01). COMT inhibition by entacapone was higher in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> than in <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>LL<\/jats:italic><\/jats:sup> patients (\u22120.54 \u00b1 0.07 vs \u22120.31 \u00b1 0.06 pmol\/min\/mg protein, <jats:italic>p<\/jats:italic> = 0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The <jats:italic>COMT<\/jats:italic><jats:sup><jats:italic>HH<\/jats:italic><\/jats:sup> genotype in PD patients enhances the effect of entacapone on the pharmacodynamics and pharmacokinetics of levodopa. The response to entacapone after repeated administrations and in heterozygous patients remains to be determined. ANN NEUROL 2011;;69:111\u2013118.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.22155","type":"journal-article","created":{"date-parts":[[2010,12,6]],"date-time":"2010-12-06T13:48:24Z","timestamp":1291643304000},"page":"111-118","source":"Crossref","is-referenced-by-count":93,"title":["The <i>COMT<\/i> Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical 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