ParkinsonFranceV1, Main, Merge, bibRecord, 001891

The COMT Val158Met Polymorphism Affects the Response to Entacapone in Parkinson's Disease: A Randomized Crossover Clinical Trial

Identifieur interne : 001891 ( Main/Merge ); précédent : 001890; suivant : 001892

The COMT Val158Met Polymorphism Affects the Response to Entacapone in Parkinson's Disease: A Randomized Crossover Clinical Trial

Auteurs : Jean-Christophe Corvol [France] ; Cécilia Bonnet [France] ; Fanny Charbonnier-Beaupel [France] ; Anne-Marie Bonnet [France] ; Marie-Hélène Fievet [France] ; Agnès Bellanger [France] ; Emmanuel Roze [France] ; Gayané Meliksetyan [France] ; MOUNA BEN DJEBARA [France] ; Andreas Hartmann [France] ; Lucette Lacomblez [France] ; Cédric Vrignaud [France] ; Noël Zahr [France] ; Yves Agid [France] ; Jean Costentin [France] ; Jean-Sébastien Hulot [France] ; Marie Vidailhet [France]

Source :

Annals of neurology [ 0364-5134 ] ; 2011.

RBID : Pascal:11-0104009

Descripteurs français

Pascal (Inist)
- Maladie de Parkinson, Pathologie du système nerveux, Polymorphisme, Entacapone, Essai clinique.

English descriptors

KwdEn :
- Clinical trial, Entacapone, Nervous system diseases, Parkinson disease, Polymorphism.

Abstract

Objective: In Parkinson disease (PD), the selective C-O-methyltransferase (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, COMT^HH), intermediate (Val/Met, COMT^HL), or low (Met/Met, COMT^LL). The objective of this study was to determine the response to entacapone in COMT^HH and COMT^LL PD patients. Methods: Thirty-three PD patients, homozygous for the COMT alleles COMT^HH (n = 17) and COMT^LL (n = 16), were randomized in a double-blind 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. Results: The gain in the best ON time was higher in COMT^HH than in COMT^LL patients (39 ± 10 vs 9 ± 9 minutes, p = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in COMT^HH than in COM^LL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMT^HHthan in COMT^LL patients (-0.54 ± 0.07 vs -0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMT^HH 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.

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Le document en format XML

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</placeName>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
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<sZ>1 aut.</sZ>
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</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
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</affiliation>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
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<s3>FRA</s3>
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<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">INIST</idno>
<idno type="inist">11-0104009</idno>
<date when="2011">2011</date>
<idno type="stanalyst">PASCAL 11-0104009 INIST</idno>
<idno type="RBID">Pascal:11-0104009</idno>
<idno type="wicri:Area/PascalFrancis/Corpus">000434</idno>
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<idno type="wicri:Area/PascalFrancis/Checkpoint">000301</idno>
<idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000301</idno>
<idno type="wicri:doubleKey">0364-5134:2011:Corvol J:the:comt:val</idno>
<idno type="wicri:Area/Main/Merge">001891</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">The COMT Val158Met Polymorphism Affects the Response to Entacapone in Parkinson's Disease: A Randomized Crossover Clinical Trial</title>
<author><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
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</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pharmacology, Pitié-Salpêtrière hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Assistance Publique Hôpitaux de Paris</wicri:noRegion>
<wicri:noRegion>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bonnet, Cecilia" sort="Bonnet, Cecilia" uniqKey="Bonnet C" first="Cécilia" last="Bonnet">Cécilia Bonnet</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Charbonnier Beaupel, Fanny" sort="Charbonnier Beaupel, Fanny" uniqKey="Charbonnier Beaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bonnet, Anne Marie" sort="Bonnet, Anne Marie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fievet, Marie Helene" sort="Fievet, Marie Helene" uniqKey="Fievet M" first="Marie-Hélène" last="Fievet">Marie-Hélène Fievet</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Assistance Publique Hôpitaux de Paris</wicri:noRegion>
<wicri:noRegion>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bellanger, Agnes" sort="Bellanger, Agnes" uniqKey="Bellanger A" first="Agnès" last="Bellanger">Agnès Bellanger</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Assistance Publique Hôpitaux de Paris</wicri:noRegion>
<wicri:noRegion>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
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<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute)</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>7 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meliksetyan, Gayane" sort="Meliksetyan, Gayane" uniqKey="Meliksetyan G" first="Gayané" last="Meliksetyan">Gayané Meliksetyan</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mouna Ben Djebara" sort="Mouna Ben Djebara" uniqKey="Mouna Ben Djebara" last="Mouna Ben Djebara">MOUNA BEN DJEBARA</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>3 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>3 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute)</s1>
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<s3>FRA</s3>
<sZ>7 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pharmacology, Pitié-Salpêtrière hospital</s1>
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<sZ>1 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>UPMC (Pierre and Marie Curie university)</s1>
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<sZ>11 aut.</sZ>
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<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
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</placeName>
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<affiliation wicri:level="3"><inist:fA14 i1="07"><s1>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vrignaud, Cedric" sort="Vrignaud, Cedric" uniqKey="Vrignaud C" first="Cédric" last="Vrignaud">Cédric Vrignaud</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pharmacology, Pitié-Salpêtrière hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noël" last="Zahr">Noël Zahr</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pharmacology, Pitié-Salpêtrière hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
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</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
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<sZ>3 aut.</sZ>
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<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>UPMC (Pierre and Marie Curie university)</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
<placeName><settlement type="city">Paris</settlement>
<region type="region" nuts="2">Île-de-France</region>
</placeName>
<orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName>
</affiliation>
</author>
<author><name sortKey="Costentin, Jean" sort="Costentin, Jean" uniqKey="Costentin J" first="Jean" last="Costentin">Jean Costentin</name>
<affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Neuropharmacology Laboratory, University of Rouen</s1>
<s2>Rouen</s2>
<s3>FRA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Région Normandie</region>
<region type="old region">Haute-Normandie</region>
<settlement type="city">Rouen</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hulot, Jean Sebastien" sort="Hulot, Jean Sebastien" uniqKey="Hulot J" first="Jean-Sébastien" last="Hulot">Jean-Sébastien Hulot</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Department of Pharmacology, Pitié-Salpêtrière hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>UPMC (Pierre and Marie Curie university)</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<affiliation wicri:level="3"><inist:fA14 i1="01"><s1>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC-9503), Pitié-Salpêtrière Hospital</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</s1>
<s3>FRA</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Department of Neurology</wicri:noRegion>
<wicri:noRegion>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="05"><s1>UPMC (Pierre and Marie Curie university)</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute)</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>7 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Annals of neurology</title>
<title level="j" type="abbreviated">Ann. neurol.</title>
<idno type="ISSN">0364-5134</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Annals of neurology</title>
<title level="j" type="abbreviated">Ann. neurol.</title>
<idno type="ISSN">0364-5134</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Clinical trial</term>
<term>Entacapone</term>
<term>Nervous system diseases</term>
<term>Parkinson disease</term>
<term>Polymorphism</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Pathologie du   système nerveux</term>
<term>Polymorphisme</term>
<term>Entacapone</term>
<term>Essai clinique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objective: In Parkinson disease (PD), the selective C-O-methyltransferase (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, COMT<sup>HH</sup>
), intermediate (Val/Met, COMT<sup>HL</sup>
), or low (Met/Met, COMT<sup>LL</sup>
). The objective of this study was to determine the response to entacapone in COMT<sup>HH</sup>
 and COMT<sup>LL</sup>
 PD patients. Methods: Thirty-three PD patients, homozygous for the COMT alleles COMT<sup>HH</sup>
 (n = 17) and COMT<sup>LL</sup>
 (n = 16), were randomized in a double-blind 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. Results: The gain in the best ON time was higher in COMT<sup>HH</sup>
 than in COMT<sup>LL</sup>
 patients (39 ± 10 vs 9 ± 9 minutes, p = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in COMT<sup>HH</sup>
 than in COM<sup>LL</sup>
 patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMT<sup>HH </sup>
than in COMT<sup>LL</sup>
 patients (-0.54 ± 0.07 vs -0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMT<sup>HH</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.</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
<region><li>Haute-Normandie</li>
<li>Région Normandie</li>
<li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
<li>Rouen</li>
</settlement>
<orgName><li>Hôpital de la Salpêtrière</li>
<li>Université Pierre-et-Marie-Curie</li>
</orgName>
</list>
<tree><country name="France"><region name="Île-de-France"><name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
</region>
<name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name>
<name sortKey="Bellanger, Agnes" sort="Bellanger, Agnes" uniqKey="Bellanger A" first="Agnès" last="Bellanger">Agnès Bellanger</name>
<name sortKey="Bonnet, Anne Marie" sort="Bonnet, Anne Marie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name>
<name sortKey="Bonnet, Cecilia" sort="Bonnet, Cecilia" uniqKey="Bonnet C" first="Cécilia" last="Bonnet">Cécilia Bonnet</name>
<name sortKey="Charbonnier Beaupel, Fanny" sort="Charbonnier Beaupel, Fanny" uniqKey="Charbonnier Beaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name>
<name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
<name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
<name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
<name sortKey="Costentin, Jean" sort="Costentin, Jean" uniqKey="Costentin J" first="Jean" last="Costentin">Jean Costentin</name>
<name sortKey="Fievet, Marie Helene" sort="Fievet, Marie Helene" uniqKey="Fievet M" first="Marie-Hélène" last="Fievet">Marie-Hélène Fievet</name>
<name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
<name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
<name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name>
<name sortKey="Hulot, Jean Sebastien" sort="Hulot, Jean Sebastien" uniqKey="Hulot J" first="Jean-Sébastien" last="Hulot">Jean-Sébastien Hulot</name>
<name sortKey="Hulot, Jean Sebastien" sort="Hulot, Jean Sebastien" uniqKey="Hulot J" first="Jean-Sébastien" last="Hulot">Jean-Sébastien Hulot</name>
<name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name>
<name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name>
<name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name>
<name sortKey="Meliksetyan, Gayane" sort="Meliksetyan, Gayane" uniqKey="Meliksetyan G" first="Gayané" last="Meliksetyan">Gayané Meliksetyan</name>
<name sortKey="Mouna Ben Djebara" sort="Mouna Ben Djebara" uniqKey="Mouna Ben Djebara" last="Mouna Ben Djebara">MOUNA BEN DJEBARA</name>
<name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name>
<name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name>
<name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name>
<name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name>
<name sortKey="Vrignaud, Cedric" sort="Vrignaud, Cedric" uniqKey="Vrignaud C" first="Cédric" last="Vrignaud">Cédric Vrignaud</name>
<name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noël" last="Zahr">Noël Zahr</name>
</country>
</tree>
</affiliations>
</record>

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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

The COMT Val158Met Polymorphism Affects the Response to Entacapone in Parkinson's Disease: A Randomized Crossover Clinical Trial

The COMT Val158Met Polymorphism Affects the Response to Entacapone in Parkinson's Disease: A Randomized Crossover Clinical Trial

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