Pharmacokinetics of apomorphine in parkinsonian patients
Identifieur interne : 002A47 ( Main/Corpus ); précédent : 002A46; suivant : 002A48Pharmacokinetics of apomorphine in parkinsonian patients
Auteurs : E. Nicolle ; P. Pollak ; F. Serre-Debeauvais ; P. Richard ; Cl Gervason ; E. Broussolle ; M. GavendSource :
- Fundamental & Clinical Pharmacology [ 0767-3981 ] ; 1993-07.
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Abstract
Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.
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DOI: 10.1111/j.1472-8206.1993.tb00238.x
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Richard</name><affiliation><mods:affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Gervason, Cl" sort="Gervason, Cl" uniqKey="Gervason C" first="Cl" last="Gervason">Cl Gervason</name><affiliation><mods:affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Broussolle, E" sort="Broussolle, E" uniqKey="Broussolle E" first="E." last="Broussolle">E. Broussolle</name><affiliation><mods:affiliation>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</mods:affiliation></affiliation></author><author><name sortKey="Gavend, M" sort="Gavend, M" uniqKey="Gavend M" first="M." last="Gavend">M. 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Nicolle</name><affiliation><mods:affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Pollak, P" sort="Pollak, P" uniqKey="Pollak P" first="P." last="Pollak">P. Pollak</name><affiliation><mods:affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Serre Ebeauvais, F" sort="Serre Ebeauvais, F" uniqKey="Serre Ebeauvais F" first="F." last="Serre-Debeauvais">F. Serre-Debeauvais</name><affiliation><mods:affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Richard, P" sort="Richard, P" uniqKey="Richard P" first="P." last="Richard">P. Richard</name><affiliation><mods:affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Gervason, Cl" sort="Gervason, Cl" uniqKey="Gervason C" first="Cl" last="Gervason">Cl Gervason</name><affiliation><mods:affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author><author><name sortKey="Broussolle, E" sort="Broussolle, E" uniqKey="Broussolle E" first="E." last="Broussolle">E. Broussolle</name><affiliation><mods:affiliation>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</mods:affiliation></affiliation></author><author><name sortKey="Gavend, M" sort="Gavend, M" uniqKey="Gavend M" first="M." last="Gavend">M. Gavend</name><affiliation><mods:affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Fundamental & Clinical Pharmacology</title><idno type="ISSN">0767-3981</idno><idno type="eISSN">1472-8206</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1993-07">1993-07</date><biblScope unit="volume">7</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="245">245</biblScope><biblScope unit="page" to="252">252</biblScope></imprint><idno type="ISSN">0767-3981</idno></series><idno type="istex">535456BF275B78EC56EF5CDD91EBF6476D34B2EC</idno><idno type="DOI">10.1111/j.1472-8206.1993.tb00238.x</idno><idno type="ArticleID">FCP238</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0767-3981</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>apomorphine</term><term>bolus injection</term><term>continuous SC infusion</term><term>human pharmacokinetics</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>E. Nicolle</name><affiliations><json:string>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item><json:item><name>P. Pollak</name><affiliations><json:string>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item><json:item><name>F. Serre‐Debeauvais</name><affiliations><json:string>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item><json:item><name>P. Richard</name><affiliations><json:string>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item><json:item><name>CL Gervason</name><affiliations><json:string>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item><json:item><name>E. Broussolle</name><affiliations><json:string>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</json:string></affiliations></json:item><json:item><name>M. Gavend</name><affiliations><json:string>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>apomorphine</value></json:item><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>human pharmacokinetics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>bolus injection</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>continuous SC infusion</value></json:item></subject><articleId><json:string>FCP238</json:string></articleId><language><json:string>eng</json:string></language><abstract>Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.</abstract><qualityIndicators><score>6.79</score><pdfVersion>1.4</pdfVersion><pdfPageSize>540 x 755.759 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1517</abstractCharCount><pdfWordCount>3602</pdfWordCount><pdfCharCount>20572</pdfCharCount><pdfPageCount>8</pdfPageCount><abstractWordCount>224</abstractWordCount></qualityIndicators><title>Pharmacokinetics of apomorphine in parkinsonian 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type="first">F.</forename><surname>Serre‐Debeauvais</surname></persName><affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation></author><author><persName><forename type="first">P.</forename><surname>Richard</surname></persName><affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation></author><author><persName><forename type="first">CL</forename><surname>Gervason</surname></persName><affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation></author><author><persName><forename type="first">E.</forename><surname>Broussolle</surname></persName><affiliation>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</affiliation></author><author><persName><forename type="first">M.</forename><surname>Gavend</surname></persName><affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation></author></analytic><monogr><title level="j">Fundamental & Clinical Pharmacology</title><idno type="pISSN">0767-3981</idno><idno type="eISSN">1472-8206</idno><idno type="DOI">10.1111/(ISSN)1472-8206</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1993-07"></date><biblScope unit="volume">7</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="245">245</biblScope><biblScope unit="page" to="252">252</biblScope></imprint></monogr><idno type="istex">535456BF275B78EC56EF5CDD91EBF6476D34B2EC</idno><idno type="DOI">10.1111/j.1472-8206.1993.tb00238.x</idno><idno type="ArticleID">FCP238</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1993</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>apomorphine</term></item><item><term>Parkinson's disease</term></item><item><term>human pharmacokinetics</term></item><item><term>bolus injection</term></item><item><term>continuous SC infusion</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1993-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/535456BF275B78EC56EF5CDD91EBF6476D34B2EC/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>Blackwell Publishing Ltd</publisherName><publisherLoc>Oxford, UK</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1472-8206</doi><issn type="print">0767-3981</issn><issn type="electronic">1472-8206</issn><idGroup><id type="product" value="FCP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="FUNDAMENTAL CLINICAL PHARMACOLOGY">Fundamental & Clinical Pharmacology</title></titleGroup></publicationMeta><publicationMeta level="part" position="07005"><doi origin="wiley">10.1111/fcp.1993.7.issue-5</doi><numberingGroup><numbering type="journalVolume" number="7">7</numbering><numbering type="journalIssue" number="5">5</numbering></numberingGroup><coverDate startDate="1993-07">July 1993</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley">10.1111/j.1472-8206.1993.tb00238.x</doi><idGroup><id type="unit" value="FCP238"></id></idGroup><countGroup><count type="pageTotal" number="8"></count></countGroup><titleGroup><title type="tocHeading1">Original Article</title></titleGroup><copyright>1993 Société Française de Pharmacologie et de Thérapeutique</copyright><eventGroup><event type="firstOnline" date="2009-08-26"></event><event type="publishedOnlineFinalForm" date="2009-08-26"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.2 mode:FullText source:HeaderRef result:HeaderRef" date="2010-03-06"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:4.0.1" date="2014-03-12"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-16"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="245">245</numbering><numbering type="pageLast" number="252">252</numbering></numberingGroup><linkGroup><link type="toTypesetVersion" href="file:FCP.FCP238.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 14 October 1992; accepted 16 March 1993</unparsedEditorialHistory><countGroup><count type="referenceTotal" number="19"></count><count type="linksCrossRef" number="7"></count></countGroup><titleGroup><title type="main">Pharmacokinetics of apomorphine in parkinsonian patients</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>E.</givenNames><familyName>Nicolle</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a2"><personName><givenNames>P.</givenNames><familyName>Pollak</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>F.</givenNames><familyName>Serre‐Debeauvais</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>P.</givenNames><familyName>Richard</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a2"><personName><givenNames>CL</givenNames><familyName>Gervason</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a3"><personName><givenNames>E.</givenNames><familyName>Broussolle</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a1"><personName><givenNames>M.</givenNames><familyName>Gavend</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1" countryCode="FR"><unparsedAffiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="FR"><unparsedAffiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="FR"><unparsedAffiliation>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">apomorphine</keyword><keyword xml:id="k2">Parkinson's disease</keyword><keyword xml:id="k3">human pharmacokinetics</keyword><keyword xml:id="k4">bolus injection</keyword><keyword xml:id="k5">continuous SC infusion</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p><b>Summary—</b> Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the T<sub>max</sub> was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Pharmacokinetics of apomorphine in parkinsonian patients</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Pharmacokinetics of apomorphine in parkinsonian patients</title></titleInfo><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Nicolle</namePart><affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Pollak</namePart><affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Serre‐Debeauvais</namePart><affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.</namePart><namePart type="family">Richard</namePart><affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">CL</namePart><namePart type="family">Gervason</namePart><affiliation>Département des Neurosciences Cliniques et Biologiques, Clinique Neurologique, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Broussolle</namePart><affiliation>Service de Neurologie, Hôpital de l'Antiquaille, 69321 Lyon Cedex 5, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Gavend</namePart><affiliation>Laboratoire de Pharmacologie, Centre Hospitalier Universitaire de Grenoble, BP 217, 38043 Grenoble Cedex 9, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><place><placeTerm type="text">Oxford, UK</placeTerm></place><dateIssued encoding="w3cdtf">1993-07</dateIssued><edition>Received 14 October 1992; accepted 16 March 1993</edition><copyrightDate encoding="w3cdtf">1993</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">19</extent></physicalDescription><abstract lang="en">Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa‐induced on‐off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high‐performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half‐life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter‐subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half‐life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.</abstract><subject lang="en"><genre>Keywords</genre><topic>apomorphine</topic><topic>Parkinson's disease</topic><topic>human pharmacokinetics</topic><topic>bolus injection</topic><topic>continuous SC infusion</topic></subject><relatedItem type="host"><titleInfo><title>Fundamental & Clinical Pharmacology</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0767-3981</identifier><identifier type="eISSN">1472-8206</identifier><identifier type="DOI">10.1111/(ISSN)1472-8206</identifier><identifier type="PublisherID">FCP</identifier><part><date>1993</date><detail type="volume"><caption>vol.</caption><number>7</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>245</start><end>252</end><total>8</total></extent></part></relatedItem><identifier type="istex">535456BF275B78EC56EF5CDD91EBF6476D34B2EC</identifier><identifier type="DOI">10.1111/j.1472-8206.1993.tb00238.x</identifier><identifier type="ArticleID">FCP238</identifier><accessCondition type="use and reproduction" contentType="copyright">1993 Société Française de Pharmacologie et de Thérapeutique</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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