Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease
Identifieur interne : 000261 ( Main/Corpus ); précédent : 000260; suivant : 000262Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease
Auteurs : Chen ; Swope ; Dashtipour ; LyonsSource :
- Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy [ 0277-0008 ] ; 2009-12.
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- KwdEn :
Abstract
Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D2 and D3 receptors. With once‐daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine‐receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2–3 weeks, and the once‐daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early‐to‐advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.
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DOI: 10.1592/phco.29.12.1452
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ISTEX:BB2DC33537842199BCD031BACB92FD2ADBFA67F8Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease</title><author><name sortKey="Chen" sort="Chen" uniqKey="Chen" last="Chen">Chen</name><affiliation><mods:affiliation>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Swope" sort="Swope" uniqKey="Swope" last="Swope">Swope</name><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Dashtipour" sort="Dashtipour" uniqKey="Dashtipour" last="Dashtipour">Dashtipour</name><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Lyons" sort="Lyons" uniqKey="Lyons" last="Lyons">Lyons</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BB2DC33537842199BCD031BACB92FD2ADBFA67F8</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1592/phco.29.12.1452</idno><idno type="url">https://api.istex.fr/document/BB2DC33537842199BCD031BACB92FD2ADBFA67F8/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000261</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease</title><author><name sortKey="Chen" sort="Chen" uniqKey="Chen" last="Chen">Chen</name><affiliation><mods:affiliation>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Swope" sort="Swope" uniqKey="Swope" last="Swope">Swope</name><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Dashtipour" sort="Dashtipour" uniqKey="Dashtipour" last="Dashtipour">Dashtipour</name><affiliation><mods:affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</mods:affiliation></affiliation></author><author><name sortKey="Lyons" sort="Lyons" uniqKey="Lyons" last="Lyons">Lyons</name><affiliation><mods:affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy</title><idno type="ISSN">0277-0008</idno><idno type="eISSN">1875-9114</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-12">2009-12</date><biblScope unit="volume">29</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1452">1452</biblScope><biblScope unit="page" to="1467">1467</biblScope></imprint><idno type="ISSN">0277-0008</idno></series><idno type="istex">BB2DC33537842199BCD031BACB92FD2ADBFA67F8</idno><idno type="DOI">10.1592/phco.29.12.1452</idno><idno type="ArticleID">PHAR544</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0277-0008</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>DRA</term><term>Parkinson's disease</term><term>RLS</term><term>dopamine‐receptor agonist</term><term>restless legs syndrome</term><term>rotigotine</term><term>transdermal administration</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D2 and D3 receptors. With once‐daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine‐receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2–3 weeks, and the once‐daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early‐to‐advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Dr. Chen Pharm.D., FCCP, BCPS, CGP</name><affiliations><json:string>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</json:string><json:string>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</json:string></affiliations></json:item><json:item><name>Dr. Swope M.D.</name><affiliations><json:string>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</json:string></affiliations></json:item><json:item><name>Dr. Dashtipour M.D., Ph.D.</name><affiliations><json:string>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</json:string></affiliations></json:item><json:item><name>Dr. Lyons Ph.D.</name><affiliations><json:string>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dopamine‐receptor agonist</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DRA</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>restless legs syndrome</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RLS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>rotigotine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>transdermal administration</value></json:item></subject><articleId><json:string>PHAR544</json:string></articleId><language><json:string>eng</json:string></language><abstract>Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. 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The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. 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School of Pharmacy, Loma Linda University, 11262 Campus Street, West Hall, Loma Linda, CA 92350; e‐mail: .</p></note><affiliation>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</affiliation><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation></author><author><persName><surname>Swope</surname></persName><roleName type="degree">Dr.</roleName><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation></author><author><persName><surname>Dashtipour</surname></persName><roleName type="degree">Dr.</roleName><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation></author><author><persName><surname>Lyons</surname></persName><roleName type="degree">Dr.</roleName><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</affiliation></author></analytic><monogr><title level="j">Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy</title><idno type="pISSN">0277-0008</idno><idno type="eISSN">1875-9114</idno><idno type="DOI">10.1002/(ISSN)1875-9114</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2009-12"></date><biblScope unit="volume">29</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1452">1452</biblScope><biblScope unit="page" to="1467">1467</biblScope></imprint></monogr><idno type="istex">BB2DC33537842199BCD031BACB92FD2ADBFA67F8</idno><idno type="DOI">10.1592/phco.29.12.1452</idno><idno type="ArticleID">PHAR544</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D2 and D3 receptors. With once‐daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine‐receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2–3 weeks, and the once‐daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. 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School of Pharmacy, Loma Linda University, 11262 Campus Street, West Hall, Loma Linda, CA 92350; e‐mail: <email>jjchen@llu.edu</email>.</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:PHAR.PHAR544.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="referenceTotal" number="75"></count><count type="linksCrossRef" number="6"></count></countGroup><titleGroup><title type="main">Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1 #a2" corresponding="yes"><personName><honorifics>Dr.</honorifics><givenNames>Jack J.</givenNames><familyName>Chen</familyName><degrees>Pharm.D., FCCP, BCPS, CGP</degrees></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a2"><personName><honorifics>Dr.</honorifics><givenNames>David M.</givenNames><familyName>Swope</familyName><degrees>M.D.</degrees></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><honorifics>Dr.</honorifics><givenNames>Khashayar</givenNames><familyName>Dashtipour</familyName><degrees>M.D., Ph.D.</degrees></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a3"><personName><honorifics>Dr.</honorifics><givenNames>Kelly E.</givenNames><familyName>Lyons</familyName><degrees>Ph.D.</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="US"><unparsedAffiliation>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="US"><unparsedAffiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="US"><unparsedAffiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">Parkinson's disease</keyword><keyword xml:id="k2">dopamine‐receptor agonist</keyword><keyword xml:id="k3">DRA</keyword><keyword xml:id="k4">restless legs syndrome</keyword><keyword xml:id="k5">RLS</keyword><keyword xml:id="k6">rotigotine</keyword><keyword xml:id="k7">transdermal administration</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p>Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D<sub>2</sub> and D<sub>3</sub> receptors. With once‐daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine‐receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2–3 weeks, and the once‐daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early‐to‐advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Transdermal Rotigotine: A Clinically Innovative Dopamine‐Receptor Agonist for the Management of Parkinson's Disease</title></titleInfo><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="family">Chen</namePart><namePart type="termsOfAddress">Pharm.D., FCCP, BCPS, CGP</namePart><affiliation>Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California.</affiliation><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation><description>Correspondence: . School of Pharmacy, Loma Linda University, 11262 Campus Street, West Hall, Loma Linda, CA 92350; e‐mail: .</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="family">Swope</namePart><namePart type="termsOfAddress">M.D.</namePart><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="family">Dashtipour</namePart><namePart type="termsOfAddress">M.D., Ph.D.</namePart><affiliation>Movement Disorders Center, Department of Neurology, School of Medicine, Loma Linda University, Loma Linda, California.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="termsOfAddress">Dr.</namePart><namePart type="family">Lyons</namePart><namePart type="termsOfAddress">Ph.D.</namePart><affiliation>Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="miscellaneous"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">2009-12</dateIssued><copyrightDate encoding="w3cdtf">2009</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="references">75</extent></physicalDescription><abstract lang="en">Rotigotine is a highly lipophilic dopamine‐receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce “off” hours in levodopa‐treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D2 and D3 receptors. With once‐daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine‐receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2–3 weeks, and the once‐daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24‐hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine‐receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early‐to‐advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.</abstract><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>dopamine‐receptor agonist</topic><topic>DRA</topic><topic>restless legs syndrome</topic><topic>RLS</topic><topic>rotigotine</topic><topic>transdermal administration</topic></subject><relatedItem type="host"><titleInfo><title>Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0277-0008</identifier><identifier type="eISSN">1875-9114</identifier><identifier type="DOI">10.1002/(ISSN)1875-9114</identifier><identifier type="PublisherID">PHAR</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>29</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1452</start><end>1467</end><total>16</total></extent></part></relatedItem><identifier type="istex">BB2DC33537842199BCD031BACB92FD2ADBFA67F8</identifier><identifier type="DOI">10.1592/phco.29.12.1452</identifier><identifier type="ArticleID">PHAR544</identifier><accessCondition type="use and reproduction" contentType="copyright">2009 Pharmacotherapy Publications Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Ltd</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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