The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial
Identifieur interne : 000F68 ( Main/Corpus ); précédent : 000F67; suivant : 000F69The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial
Auteurs : Jean-Christophe Corvol ; Cécilia Bonnet ; Fanny Charbonnier-Beaupel ; Anne-Marie Bonnet ; Marie-Hélène Fiévet ; Agnès Bellanger ; Emmanuel Roze ; Gayané Meliksetyan ; Mouna Ben Djebara ; Andreas Hartmann ; Lucette Lacomblez ; Cédric Vrignaud ; Noël Zahr ; Yves Agid ; Jean Costentin ; Jean-Sébastien Hulot ; Marie VidailhetSource :
- Annals of Neurology [ 0364-5134 ] ; 2011-01.
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, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods: Thirty‐three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (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 COMTHH than in COMTLL 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 COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMTHH 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;;69:111–118.
Url:
DOI: 10.1002/ana.22155
Links to Exploration step
ISTEX:B5DD2B27B16748C39AFFC4F06B24BA888850268ELe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title><author><name sortKey="Corvol, Jean Hristophe" sort="Corvol, Jean Hristophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Bonnet, Cecilia" sort="Bonnet, Cecilia" uniqKey="Bonnet C" first="Cécilia" last="Bonnet">Cécilia Bonnet</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Charbonnier Eaupel, Fanny" sort="Charbonnier Eaupel, Fanny" uniqKey="Charbonnier Eaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bonnet, Anne Arie" sort="Bonnet, Anne Arie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Fievet, Marie Elene" sort="Fievet, Marie Elene" uniqKey="Fievet M" first="Marie-Hélène" last="Fiévet">Marie-Hélène Fiévet</name><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Bellanger, Agnes" sort="Bellanger, Agnes" uniqKey="Bellanger A" first="Agnès" last="Bellanger">Agnès Bellanger</name><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Meliksetyan, Gayane" sort="Meliksetyan, Gayane" uniqKey="Meliksetyan G" first="Gayané" last="Meliksetyan">Gayané Meliksetyan</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Ben Djebara, Mouna" sort="Ben Djebara, Mouna" uniqKey="Ben Djebara M" first="Mouna" last="Ben Djebara">Mouna Ben Djebara</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Vrignaud, Cedric" sort="Vrignaud, Cedric" uniqKey="Vrignaud C" first="Cédric" last="Vrignaud">Cédric Vrignaud</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noël" last="Zahr">Noël Zahr</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Costentin, Jean" sort="Costentin, Jean" uniqKey="Costentin J" first="Jean" last="Costentin">Jean Costentin</name><affiliation><mods:affiliation>Neuropharmacology Laboratory, University of Rouen, Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Hulot, Jean Ebastien" sort="Hulot, Jean Ebastien" uniqKey="Hulot J" first="Jean-Sébastien" last="Hulot">Jean-Sébastien Hulot</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B5DD2B27B16748C39AFFC4F06B24BA888850268E</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1002/ana.22155</idno><idno type="url">https://api.istex.fr/document/B5DD2B27B16748C39AFFC4F06B24BA888850268E/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000F68</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title><author><name sortKey="Corvol, Jean Hristophe" sort="Corvol, Jean Hristophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Bonnet, Cecilia" sort="Bonnet, Cecilia" uniqKey="Bonnet C" first="Cécilia" last="Bonnet">Cécilia Bonnet</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Charbonnier Eaupel, Fanny" sort="Charbonnier Eaupel, Fanny" uniqKey="Charbonnier Eaupel F" first="Fanny" last="Charbonnier-Beaupel">Fanny Charbonnier-Beaupel</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Bonnet, Anne Arie" sort="Bonnet, Anne Arie" uniqKey="Bonnet A" first="Anne-Marie" last="Bonnet">Anne-Marie Bonnet</name><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Fievet, Marie Elene" sort="Fievet, Marie Elene" uniqKey="Fievet M" first="Marie-Hélène" last="Fiévet">Marie-Hélène Fiévet</name><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Bellanger, Agnes" sort="Bellanger, Agnes" uniqKey="Bellanger A" first="Agnès" last="Bellanger">Agnès Bellanger</name><affiliation><mods:affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</mods:affiliation></affiliation></author><author><name sortKey="Roze, Emmanuel" sort="Roze, Emmanuel" uniqKey="Roze E" first="Emmanuel" last="Roze">Emmanuel Roze</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Meliksetyan, Gayane" sort="Meliksetyan, Gayane" uniqKey="Meliksetyan G" first="Gayané" last="Meliksetyan">Gayané Meliksetyan</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Ben Djebara, Mouna" sort="Ben Djebara, Mouna" uniqKey="Ben Djebara M" first="Mouna" last="Ben Djebara">Mouna Ben Djebara</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Lacomblez, Lucette" sort="Lacomblez, Lucette" uniqKey="Lacomblez L" first="Lucette" last="Lacomblez">Lucette Lacomblez</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Vrignaud, Cedric" sort="Vrignaud, Cedric" uniqKey="Vrignaud C" first="Cédric" last="Vrignaud">Cédric Vrignaud</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noël" last="Zahr">Noël Zahr</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Costentin, Jean" sort="Costentin, Jean" uniqKey="Costentin J" first="Jean" last="Costentin">Jean Costentin</name><affiliation><mods:affiliation>Neuropharmacology Laboratory, University of Rouen, Rouen, France</mods:affiliation></affiliation></author><author><name sortKey="Hulot, Jean Ebastien" sort="Hulot, Jean Ebastien" uniqKey="Hulot J" first="Jean-Sébastien" last="Hulot">Jean-Sébastien Hulot</name><affiliation><mods:affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation></author><author><name sortKey="Vidailhet, Marie" sort="Vidailhet, Marie" uniqKey="Vidailhet M" first="Marie" last="Vidailhet">Marie Vidailhet</name><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>UPMC (Pierre and Marie Curie university), Paris, France</mods:affiliation></affiliation><affiliation><mods:affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-01">2011-01</date><biblScope unit="volume">69</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="111">111</biblScope><biblScope unit="page" to="118">118</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">B5DD2B27B16748C39AFFC4F06B24BA888850268E</idno><idno type="DOI">10.1002/ana.22155</idno><idno type="ArticleID">ANA22155</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></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, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods: Thirty‐three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (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 COMTHH than in COMTLL 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 COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMTHH 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;;69:111–118.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Jean‐Christophe Corvol MD, PhD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</json:string></affiliations></json:item><json:item><name>Cécilia Bonnet MD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Fanny Charbonnier‐Beaupel PharmD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Anne‐Marie Bonnet MD</name><affiliations><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Marie‐Hélène Fiévet PharmD</name><affiliations><json:string>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</json:string></affiliations></json:item><json:item><name>Agnès Bellanger PharmD</name><affiliations><json:string>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</json:string></affiliations></json:item><json:item><name>Emmanuel Roze MD, PhD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</json:string></affiliations></json:item><json:item><name>Gayané Meliksetyan MD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Mouna Ben Djebara MD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Andreas Hartmann MD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</json:string></affiliations></json:item><json:item><name>Lucette Lacomblez MD</name><affiliations><json:string>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>UPMC (Pierre and Marie Curie university), Paris, France</json:string><json:string>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</json:string></affiliations></json:item><json:item><name>Cédric Vrignaud BSc</name><affiliations><json:string>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Noël Zahr PhD</name><affiliations><json:string>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</json:string></affiliations></json:item><json:item><name>Yves Agid MD, PhD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>UPMC (Pierre and Marie Curie university), Paris, France</json:string></affiliations></json:item><json:item><name>Jean Costentin MD</name><affiliations><json:string>Neuropharmacology Laboratory, University of Rouen, Rouen, France</json:string></affiliations></json:item><json:item><name>Jean‐Sébastien Hulot MD, PhD</name><affiliations><json:string>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>UPMC (Pierre and Marie Curie university), Paris, France</json:string></affiliations></json:item><json:item><name>Marie Vidailhet MD</name><affiliations><json:string>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</json:string><json:string>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</json:string><json:string>UPMC (Pierre and Marie Curie university), Paris, France</json:string><json:string>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</json:string></affiliations></json:item></author><articleId><json:string>ANA22155</json:string></articleId><language><json:string>eng</json:string></language><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, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods: Thirty‐three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (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 COMTHH than in COMTLL 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 COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMTHH 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;;69:111–118.</abstract><qualityIndicators><score>7.216</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 801 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1636</abstractCharCount><pdfWordCount>4216</pdfWordCount><pdfCharCount>27230</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>253</abstractWordCount></qualityIndicators><title>The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title><genre><json:string>article</json:string></genre><host><volume>69</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>1</total><last>118</last><first>111</first></pages><issn><json:string>0364-5134</json:string></issn><issue>1</issue><subject><json:item><value>Original Article</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1002/ana.22155</json:string></doi><id>B5DD2B27B16748C39AFFC4F06B24BA888850268E</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/B5DD2B27B16748C39AFFC4F06B24BA888850268E/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/B5DD2B27B16748C39AFFC4F06B24BA888850268E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B5DD2B27B16748C39AFFC4F06B24BA888850268E/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title><author><persName><forename type="first">Jean‐Christophe</forename><surname>Corvol</surname></persName><roleName type="degree">MD, PhD</roleName><note type="correspondence"><p>Correspondence: Centre d'Investigation Clinique, Hôpital pitié‐Salpêtrière, 47/83 Bd de l'Hôpital, 75013 Paris, France</p></note><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation></author><author><persName><forename type="first">Cécilia</forename><surname>Bonnet</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation></author><author><persName><forename type="first">Fanny</forename><surname>Charbonnier‐Beaupel</surname></persName><roleName type="degree">PharmD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation></author><author><persName><forename type="first">Anne‐Marie</forename><surname>Bonnet</surname></persName><roleName type="degree">MD</roleName><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation></author><author><persName><forename type="first">Marie‐Hélène</forename><surname>Fiévet</surname></persName><roleName type="degree">PharmD</roleName><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation></author><author><persName><forename type="first">Agnès</forename><surname>Bellanger</surname></persName><roleName type="degree">PharmD</roleName><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation></author><author><persName><forename type="first">Emmanuel</forename><surname>Roze</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation></author><author><persName><forename type="first">Gayané</forename><surname>Meliksetyan</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation></author><author><persName><forename type="first">Mouna</forename><surname>Ben Djebara</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation></author><author><persName><forename type="first">Andreas</forename><surname>Hartmann</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation></author><author><persName><forename type="first">Lucette</forename><surname>Lacomblez</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</affiliation></author><author><persName><forename type="first">Cédric</forename><surname>Vrignaud</surname></persName><roleName type="degree">BSc</roleName><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation></author><author><persName><forename type="first">Noël</forename><surname>Zahr</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation></author><author><persName><forename type="first">Yves</forename><surname>Agid</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation></author><author><persName><forename type="first">Jean</forename><surname>Costentin</surname></persName><roleName type="degree">MD</roleName><affiliation>Neuropharmacology Laboratory, University of Rouen, Rouen, France</affiliation></author><author><persName><forename type="first">Jean‐Sébastien</forename><surname>Hulot</surname></persName><roleName type="degree">MD, PhD</roleName><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation></author><author><persName><forename type="first">Marie</forename><surname>Vidailhet</surname></persName><roleName type="degree">MD</roleName><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-01"></date><biblScope unit="volume">69</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="111">111</biblScope><biblScope unit="page" to="118">118</biblScope></imprint></monogr><idno type="istex">B5DD2B27B16748C39AFFC4F06B24BA888850268E</idno><idno type="DOI">10.1002/ana.22155</idno><idno type="ArticleID">ANA22155</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods: Thirty‐three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (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 COMTHH than in COMTLL 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 COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMTHH 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;;69:111–118.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>article category</head><item><term>Original Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-05-28">Received</change><change when="2010-07-09">Registration</change><change when="2011-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/B5DD2B27B16748C39AFFC4F06B24BA888850268E/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8249</doi><issn type="print">0364-5134</issn><issn type="electronic">1531-8249</issn><idGroup><id type="product" value="ANA"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="ANNALS OF NEUROLOGY">Annals of Neurology</title><title type="short">Ann Neurol.</title></titleGroup></publicationMeta><publicationMeta level="part" position="10"><doi origin="wiley" registered="yes">10.1002/ana.v69.1</doi><numberingGroup><numbering type="journalVolume" number="69">69</numbering><numbering type="journalIssue">1</numbering></numberingGroup><coverDate startDate="2011-01">January 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="190" status="forIssue"><doi origin="wiley" registered="yes">10.1002/ana.22155</doi><idGroup><id type="unit" value="ANA22155"></id></idGroup><countGroup><count type="pageTotal" number="1"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="publisher">Copyright © 2010 American Neurological Association</copyright><eventGroup><event type="manuscriptReceived" date="2010-05-28"></event><event type="manuscriptRevised" date="2010-07-04"></event><event type="manuscriptAccepted" date="2010-07-09"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.4.4 mode:FullText" date="2011-01-28"></event><event type="publishedOnlineAccepted" date="2010-12-06"></event><event type="firstOnline" date="2011-01-28"></event><event type="publishedOnlineFinalForm" date="2011-01-28"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">111</numbering><numbering type="pageLast">118</numbering></numberingGroup><correspondenceTo>Centre d'Investigation Clinique, Hôpital pitié‐Salpêtrière, 47/83 Bd de l'Hôpital, 75013 Paris, France</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA22155.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="25"></count><count type="wordTotal" number="0"></count></countGroup><titleGroup><title type="main" xml:lang="en">The <i>COMT</i> Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title><title type="short" xml:lang="en">COMT and Entacapone in PD</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2 #af3 #af4" corresponding="yes"><personName><givenNames>Jean‐Christophe</givenNames><familyName>Corvol</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email normalForm="jean-christophe.corvol@psl.aphp.fr">jean‐christophe.corvol@psl.aphp.fr</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Cécilia</givenNames><familyName>Bonnet</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Fanny</givenNames><familyName>Charbonnier‐Beaupel</familyName><degrees>PharmD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Anne‐Marie</givenNames><familyName>Bonnet</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Marie‐Hélène</givenNames><familyName>Fiévet</familyName><degrees>PharmD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Agnès</givenNames><familyName>Bellanger</familyName><degrees>PharmD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1 #af2 #af6"><personName><givenNames>Emmanuel</givenNames><familyName>Roze</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Gayané</givenNames><familyName>Meliksetyan</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Mouna</givenNames><familyName>Ben Djebara</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1 #af2 #af6"><personName><givenNames>Andreas</givenNames><familyName>Hartmann</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au11" creatorRole="author" affiliationRef="#af3 #af5 #af7"><personName><givenNames>Lucette</givenNames><familyName>Lacomblez</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au12" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Cédric</givenNames><familyName>Vrignaud</familyName><degrees>BSc</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Noël</givenNames><familyName>Zahr</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1 #af2 #af5"><personName><givenNames>Yves</givenNames><familyName>Agid</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Jean</givenNames><familyName>Costentin</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au16" creatorRole="author" affiliationRef="#af3 #af5"><personName><givenNames>Jean‐Sébastien</givenNames><familyName>Hulot</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au17" creatorRole="author" affiliationRef="#af1 #af2 #af5 #af6"><personName><givenNames>Marie</givenNames><familyName>Vidailhet</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="FR" type="organization"><unparsedAffiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="FR" type="organization"><unparsedAffiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="FR" type="organization"><unparsedAffiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="FR" type="organization"><unparsedAffiliation>UPMC (Pierre and Marie Curie university), Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="FR" type="organization"><unparsedAffiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="FR" type="organization"><unparsedAffiliation>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="FR" type="organization"><unparsedAffiliation>Neuropharmacology Laboratory, University of Rouen, Rouen, France</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Objective</title><p>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, <i>COMT</i><sup><i>HH</i></sup>), intermediate (Val/Met, <i>COMT</i><sup><i>HL</i></sup>), or low (Met/Met, <i>COMT</i><sup><i>LL</i></sup>). The objective of this study was to determine the response to entacapone in <i>COMT</i><sup><i>HH</i></sup> and <i>COMT</i><sup><i>LL</i></sup> PD patients.</p></section><section xml:id="abs1-2"><title type="main">Methods</title><p>Thirty‐three PD patients, homozygous for the <i>COMT</i> alleles <i>COMT</i><sup><i>HH</i></sup> (n = 17) and <i>COMT</i><sup><i>LL</i></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.</p></section><section xml:id="abs1-3"><title type="main">Results</title><p>The gain in the best ON time was higher in <i>COMT</i><sup><i>HH</i></sup> than in <i>COMT</i><sup><i>LL</i></sup> patients (39 ± 10 vs 9 ± 9 minutes, <i>p</i> = 0.04, interaction between treatment and genotype). Area under the concentration over time curve of levodopa increased more after entacapone in <i>COMT</i><sup><i>HH</i></sup> than in <i>COMT</i><sup><i>LL</i></sup> patients (+62 ± 6% vs +34 ± 8%, <i>p</i> = 0.01). COMT inhibition by entacapone was higher in <i>COMT</i><sup><i>HH</i></sup> than in <i>COMT</i><sup><i>LL</i></sup> patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, <i>p</i> = 0.02).</p></section><section xml:id="abs1-4"><title type="main">Interpretation</title><p>The <i>COMT</i><sup><i>HH</i></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;;69:111–118.</p></section></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>COMT and Entacapone in PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The</title></titleInfo><name type="personal"><namePart type="given">Jean‐Christophe</namePart><namePart type="family">Corvol</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation><description>Correspondence: Centre d'Investigation Clinique, Hôpital pitié‐Salpêtrière, 47/83 Bd de l'Hôpital, 75013 Paris, France</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cécilia</namePart><namePart type="family">Bonnet</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Fanny</namePart><namePart type="family">Charbonnier‐Beaupel</namePart><namePart type="termsOfAddress">PharmD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne‐Marie</namePart><namePart type="family">Bonnet</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marie‐Hélène</namePart><namePart type="family">Fiévet</namePart><namePart type="termsOfAddress">PharmD</namePart><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Agnès</namePart><namePart type="family">Bellanger</namePart><namePart type="termsOfAddress">PharmD</namePart><affiliation>Department of Pharmacy, Assistance Publique Hôpitaux de Paris</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Emmanuel</namePart><namePart type="family">Roze</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gayané</namePart><namePart type="family">Meliksetyan</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mouna</namePart><namePart type="family">Ben Djebara</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Andreas</namePart><namePart type="family">Hartmann</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lucette</namePart><namePart type="family">Lacomblez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_678 unit, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cédric</namePart><namePart type="family">Vrignaud</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Noël</namePart><namePart type="family">Zahr</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yves</namePart><namePart type="family">Agid</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean</namePart><namePart type="family">Costentin</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neuropharmacology Laboratory, University of Rouen, Rouen, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean‐Sébastien</namePart><namePart type="family">Hulot</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Pharmacology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Marie</namePart><namePart type="family">Vidailhet</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM (French National Institute of Medical Research and Health), Clinical Investigation Center (CIC‐9503), Pitié‐Salpêtrière Hospital, Paris, France</affiliation><affiliation>APHP (Assistance Publique Hôpitaux de Paris, Public Hospital of Paris), Department of Neurology, Pitié‐Salpêtrière hospital, Paris, France</affiliation><affiliation>UPMC (Pierre and Marie Curie university), Paris, France</affiliation><affiliation>INSERM (French National Institute of Medical Research and Health), UMRS_975 unit, CRICM (Research Center of the Brain and Spine Insitute), Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2011-01</dateIssued><dateCaptured encoding="w3cdtf">2010-05-28</dateCaptured><dateValid encoding="w3cdtf">2010-07-09</dateValid><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">2</extent><extent unit="references">25</extent></physicalDescription><abstract 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, COMTHH), intermediate (Val/Met, COMTHL), or low (Met/Met, COMTLL). The objective of this study was to determine the response to entacapone in COMTHH and COMTLL PD patients. Methods: Thirty‐three PD patients, homozygous for the COMT alleles COMTHH (n = 17) and COMTLL (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 COMTHH than in COMTLL 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 COMTHH than in COMTLL patients (+62 ± 6% vs +34 ± 8%, p = 0.01). COMT inhibition by entacapone was higher in COMTHH than in COMTLL patients (−0.54 ± 0.07 vs −0.31 ± 0.06 pmol/min/mg protein, p = 0.02). Interpretation: The COMTHH 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;;69:111–118.</abstract><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>69</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>111</start><end>118</end><total>1</total></extent></part></relatedItem><identifier type="istex">B5DD2B27B16748C39AFFC4F06B24BA888850268E</identifier><identifier type="DOI">10.1002/ana.22155</identifier><identifier type="ArticleID">ANA22155</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F68 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 000F68 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:B5DD2B27B16748C39AFFC4F06B24BA888850268E
|texte= The COMT Val158Met polymorphism affects the response to entacapone in Parkinson's disease: A randomized crossover clinical trial
}}
| This area was generated with Dilib version V0.6.23. |  |