The effect of peripheral enzyme inhibitors on levodopa concentrations in blood and CSF.
Identifieur interne : 002975 ( Ncbi/Checkpoint ); précédent : 002974; suivant : 002976The effect of peripheral enzyme inhibitors on levodopa concentrations in blood and CSF.
Auteurs : Maria Nord [Suède] ; Peter Zsigmond ; Anita Kullman ; Kerstin Arstrand ; Nil DizdarSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2010.
English descriptors
- KwdEn :
- Administration, Oral, Aged, Aged, 80 and over, Antiparkinson Agents (blood), Antiparkinson Agents (cerebrospinal fluid), Antiparkinson Agents (therapeutic use), Area Under Curve, Catechols (administration & dosage), Dose-Response Relationship, Drug, Enzyme Inhibitors (administration & dosage), Female, Humans, Levodopa (blood), Levodopa (cerebrospinal fluid), Levodopa (therapeutic use), Male, Mepivacaine (administration & dosage), Microdialysis (methods), Middle Aged, Nitriles (administration & dosage), Parkinson Disease (blood), Parkinson Disease (cerebrospinal fluid), Parkinson Disease (drug therapy), Time Factors.
- MESH :
- chemical , administration & dosage : Catechols, Enzyme Inhibitors, Mepivacaine, Nitriles.
- chemical , blood : Antiparkinson Agents, Levodopa.
- chemical , cerebrospinal fluid : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- blood : Parkinson Disease.
- cerebrospinal fluid : Parkinson Disease.
- drug therapy : Parkinson Disease.
- methods : Microdialysis.
- Administration, Oral, Aged, Aged, 80 and over, Area Under Curve, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Time Factors.
Abstract
Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa, shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day 1; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg tid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C(max) of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C(max) in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.
DOI: 10.1002/mds.22613
PubMed: 20077469
Affiliations:
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last="Arstrand">Kerstin Arstrand</name></author><author><name sortKey="Dizdar, Nil" sort="Dizdar, Nil" uniqKey="Dizdar N" first="Nil" last="Dizdar">Nil Dizdar</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="doi">10.1002/mds.22613</idno><idno type="RBID">pubmed:20077469</idno><idno type="pmid">20077469</idno><idno type="wicri:Area/PubMed/Corpus">001A27</idno><idno type="wicri:Area/PubMed/Curation">001A27</idno><idno type="wicri:Area/PubMed/Checkpoint">001569</idno><idno type="wicri:Area/Ncbi/Merge">002975</idno><idno type="wicri:Area/Ncbi/Curation">002975</idno><idno type="wicri:Area/Ncbi/Checkpoint">002975</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The effect of peripheral enzyme inhibitors on levodopa concentrations in blood and CSF.</title><author><name sortKey="Nord, Maria" sort="Nord, Maria" uniqKey="Nord M" first="Maria" last="Nord">Maria Nord</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University Hospital, Linköping, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neurology, University Hospital, Linköping</wicri:regionArea><wicri:noRegion>Linköping</wicri:noRegion></affiliation></author><author><name sortKey="Zsigmond, Peter" sort="Zsigmond, Peter" uniqKey="Zsigmond P" first="Peter" last="Zsigmond">Peter Zsigmond</name></author><author><name sortKey="Kullman, Anita" sort="Kullman, Anita" uniqKey="Kullman A" first="Anita" last="Kullman">Anita Kullman</name></author><author><name sortKey="Arstrand, Kerstin" sort="Arstrand, Kerstin" uniqKey="Arstrand K" first="Kerstin" last="Arstrand">Kerstin Arstrand</name></author><author><name sortKey="Dizdar, Nil" sort="Dizdar, Nil" uniqKey="Dizdar N" first="Nil" last="Dizdar">Nil Dizdar</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term><term>Aged</term><term>Aged, 80 and over</term><term>Antiparkinson Agents (blood)</term><term>Antiparkinson Agents (cerebrospinal fluid)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Area Under Curve</term><term>Catechols (administration & dosage)</term><term>Dose-Response Relationship, Drug</term><term>Enzyme Inhibitors (administration & dosage)</term><term>Female</term><term>Humans</term><term>Levodopa (blood)</term><term>Levodopa (cerebrospinal fluid)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Mepivacaine (administration & dosage)</term><term>Microdialysis (methods)</term><term>Middle Aged</term><term>Nitriles (administration & dosage)</term><term>Parkinson Disease (blood)</term><term>Parkinson Disease (cerebrospinal fluid)</term><term>Parkinson Disease (drug therapy)</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Catechols</term><term>Enzyme Inhibitors</term><term>Mepivacaine</term><term>Nitriles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" 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="blood" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Microdialysis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Aged</term><term>Aged, 80 and over</term><term>Area Under Curve</term><term>Dose-Response Relationship, Drug</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa, shifts the metabolism to the COMT pathway. Adding the peripheral acting COMT inhibitor entacapone provides improvement for patients with PD suffering from motor fluctuations. We studied the effects of the enzyme inhibitors entacapone and carbidopa on the levodopa concentrations in CSF and in blood. Five PD patients with wearing-off underwent lumbar drainage and intravenous microdialysis. Samples were taken 12 h daily for 3 days. Day 1; intravenous levodopa was given, day 2; additional oral entacapone 200 mg tid, day 3; additional oral entacapone 200 mg tid and carbidopa 25 mg bid. Levodopa in CSF and in dialysates was analysed. The AUC for levodopa increased both in blood and CSF when additional entacapone was given alone and in combination with carbidopa. The C(max) of levodopa in both CSF and blood increased significantly. Additional entacapone to levodopa therapy gives an increase of C(max) in CSF and in blood. The increase is more evident when entacapone is combined with carbidopa.</div></front></TEI><affiliations><list><country><li>Suède</li></country></list><tree><noCountry><name sortKey="Arstrand, Kerstin" sort="Arstrand, Kerstin" uniqKey="Arstrand K" first="Kerstin" last="Arstrand">Kerstin Arstrand</name><name sortKey="Dizdar, Nil" sort="Dizdar, Nil" uniqKey="Dizdar N" first="Nil" last="Dizdar">Nil Dizdar</name><name sortKey="Kullman, Anita" sort="Kullman, Anita" uniqKey="Kullman A" first="Anita" last="Kullman">Anita Kullman</name><name sortKey="Zsigmond, Peter" sort="Zsigmond, Peter" uniqKey="Zsigmond P" first="Peter" last="Zsigmond">Peter Zsigmond</name></noCountry><country name="Suède"><noRegion><name sortKey="Nord, Maria" sort="Nord, Maria" uniqKey="Nord M" first="Maria" last="Nord">Maria Nord</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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