A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.
Identifieur interne : 000164 ( PubMed/Corpus ); précédent : 000163; suivant : 000165A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.
Auteurs : N. Simon ; F. Viallet ; A. Boulamery ; A. Eusebio ; D. Gayraud ; J-P AzulaySource :
- European journal of clinical pharmacology [ 1432-1041 ] ; 2016.
English descriptors
- KwdEn :
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- drug therapy : Parkinson Disease.
- etiology : Dyskinesia, Drug-Induced.
- Aged, Female, Humans, Male, Middle Aged, Models, Biological, Prospective Studies.
Abstract
Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia.
DOI: 10.1007/s00228-016-2034-0
PubMed: 26936272
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pubmed:26936272Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.</title><author><name sortKey="Simon, N" sort="Simon, N" uniqKey="Simon N" first="N" last="Simon">N. Simon</name><affiliation><nlm:affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France. nicolas.Simon@ap-hm.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Viallet, F" sort="Viallet, F" uniqKey="Viallet F" first="F" last="Viallet">F. Viallet</name><affiliation><nlm:affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</nlm:affiliation></affiliation></author><author><name sortKey="Boulamery, A" sort="Boulamery, A" uniqKey="Boulamery A" first="A" last="Boulamery">A. Boulamery</name><affiliation><nlm:affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eusebio, A" sort="Eusebio, A" uniqKey="Eusebio A" first="A" last="Eusebio">A. Eusebio</name><affiliation><nlm:affiliation>Service de Neurologie, CHU Timone, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gayraud, D" sort="Gayraud, D" uniqKey="Gayraud D" first="D" last="Gayraud">D. Gayraud</name><affiliation><nlm:affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</nlm:affiliation></affiliation></author><author><name sortKey="Azulay, J P" sort="Azulay, J P" uniqKey="Azulay J" first="J-P" last="Azulay">J-P Azulay</name><affiliation><nlm:affiliation>Service de Neurologie, CHU Timone, Marseille, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26936272</idno><idno type="pmid">26936272</idno><idno type="doi">10.1007/s00228-016-2034-0</idno><idno type="wicri:Area/PubMed/Corpus">000164</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000164</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.</title><author><name sortKey="Simon, N" sort="Simon, N" uniqKey="Simon N" first="N" last="Simon">N. Simon</name><affiliation><nlm:affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France. nicolas.Simon@ap-hm.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Viallet, F" sort="Viallet, F" uniqKey="Viallet F" first="F" last="Viallet">F. Viallet</name><affiliation><nlm:affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</nlm:affiliation></affiliation></author><author><name sortKey="Boulamery, A" sort="Boulamery, A" uniqKey="Boulamery A" first="A" last="Boulamery">A. Boulamery</name><affiliation><nlm:affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Eusebio, A" sort="Eusebio, A" uniqKey="Eusebio A" first="A" last="Eusebio">A. Eusebio</name><affiliation><nlm:affiliation>Service de Neurologie, CHU Timone, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gayraud, D" sort="Gayraud, D" uniqKey="Gayraud D" first="D" last="Gayraud">D. Gayraud</name><affiliation><nlm:affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</nlm:affiliation></affiliation></author><author><name sortKey="Azulay, J P" sort="Azulay, J P" uniqKey="Azulay J" first="J-P" last="Azulay">J-P Azulay</name><affiliation><nlm:affiliation>Service de Neurologie, CHU Timone, Marseille, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">European journal of clinical pharmacology</title><idno type="eISSN">1432-1041</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Female</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Models, Biological</term><term>Parkinson Disease (drug therapy)</term><term>Prospective Studies</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Models, Biological</term><term>Prospective Studies</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26936272</PMID><DateCreated><Year>2016</Year><Month>03</Month><Day>16</Day></DateCreated><DateCompleted><Year>2016</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>12</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-1041</ISSN><JournalIssue CitedMedium="Internet"><Volume>72</Volume><Issue>4</Issue><PubDate><Year>2016</Year><Month>Apr</Month></PubDate></JournalIssue><Title>European journal of clinical pharmacology</Title><ISOAbbreviation>Eur. J. Clin. Pharmacol.</ISOAbbreviation></Journal><ArticleTitle>A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.</ArticleTitle><Pagination><MedlinePgn>423-30</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00228-016-2034-0</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study. They received a single dose of levodopa equal to 150 % of their usual daily dose. Blood samples, motor evaluations (UPDRS III scale) and peak-dose dyskinesia (Goetz scale) were examined after administration. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed using NONMEM software.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Pharmacokinetic analysis identified a one-compartment model with the following parameter values [bootstrap 95 % CI]: absorption rate constant (KA) 1.86 1/h [1.08-3.25], clearance 36.6 L/h [31.3-42.8], and volume of distribution 42.9 L [34.3-52.3]. Between-subject variability was 122 % [71-183] and 38 % [26-47] for KA and clearance, respectively. Residual variability was 1120 μg/L [886-1290]. UPDRS III and dyskinesia were best described with an effect compartment and similar KE0 values of 1.37 1/h [1.01-1.77]. For UPDRS III, the E0, EC50, Emax, and Hill coefficient were 31.4 [28.4-35.3], 1410 μg/L [1200-1700], 0.72 [0.71-0.75], and 4.26 [3.20-5.58], respectively. For dyskinesia, the EC50 and Emax were 6280 μg/L [3420-37,900] and 17.9 [12.3-80.8], respectively. Residual variability was 3.15 [2.75-3.53] for UPDRS III and 2.66 [1.94-3.51] for dyskinesia. No covariates influenced the parameters.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">In patients treated with levodopa and suffering from dyskinesia, the motor response and dyskinesia have close onsets and duration effects. Maximal motor response tends to be inevitably associated with dyskinesia.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Simon</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France. nicolas.Simon@ap-hm.fr.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Aix-Marseille Université, INSERM UMR_S 912 (SESSTIM), IRD, 13385, Marseille, France. nicolas.Simon@ap-hm.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Viallet</LastName><ForeName>F</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire Parole et langage, Aix-Marseille Université, UMR CNRS 7309, 13003, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boulamery</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Service de Pharmacologie Clinique, AP-HM, Hôpital Sainte Marguerite, CAP-TV, 13274, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eusebio</LastName><ForeName>A</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Service de Neurologie, CHU Timone, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gayraud</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Service de neurologie, Centre Hospitalier Intercommunal Aix Pertuis, 13613, Aix-en-Provence, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Azulay</LastName><ForeName>J-P</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Service de Neurologie, CHU Timone, Marseille, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>03</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Eur J Clin Pharmacol</MedlineTA><NlmUniqueID>1256165</NlmUniqueID><ISSNLinking>0031-6970</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>46627O600J</RegistryNumber><NameOfSubstance UI="D007980">Levodopa</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000978" MajorTopicYN="N">Antiparkinson Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004409" MajorTopicYN="N">Dyskinesia, Drug-Induced</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007980" MajorTopicYN="N">Levodopa</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008954" MajorTopicYN="N">Models, Biological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Levodopa</Keyword><Keyword MajorTopicYN="N">NONMEM</Keyword><Keyword MajorTopicYN="N">Parkinson’s dyskinesia</Keyword><Keyword MajorTopicYN="N">Pharmacodynamics</Keyword><Keyword MajorTopicYN="N">Population pharmacokinetics</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year><Month>11</Month><Day>05</Day></PubMedPubDate><PubMedPubDate 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