Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease
Identifieur interne : 003631 ( Ncbi/Merge ); précédent : 003630; suivant : 003632Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease
Auteurs : Lissa S. Brod ; Jason L. Aldred ; John G. NuttSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2012.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Antiparkinson Agents (administration & dosage), Antiparkinson Agents (pharmacokinetics), Antiparkinson Agents (therapeutic use), Area Under Curve, Carbidopa (administration & dosage), Carbidopa (pharmacokinetics), Carbidopa (therapeutic use), Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Levodopa (therapeutic use), Male, Middle Aged, Parkinson Disease (drug therapy), Treatment Outcome.
- MESH :
- chemical , administration & dosage : Antiparkinson Agents, Carbidopa.
- chemical , pharmacokinetics : Antiparkinson Agents, Carbidopa.
- chemical , therapeutic use : Antiparkinson Agents, Carbidopa, Levodopa.
- drug therapy : Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Area Under Curve, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Treatment Outcome.
Abstract
Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects.
We compared 4-week outpatient treatments with carbidopa 75 mg and 450 mg/day administered with levodopa on the subjects’ normal schedule. After each treatment phase subjects had two 2-hour levodopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding four weeks and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and levodopa and carbidopa plasma concentrations were monitored during the infusions.
Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four levodopa infusions although AUC for plasma levodopa was modestly increased with 450 mg of carbidopa. Nine subjects reported the high carbidopa outpatient phase was associated with greater response to levodopa.
Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day.
Url:
DOI: 10.1002/mds.24998
PubMed: 22508376
PubMed Central: 3707928
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S." last="Brod">Lissa S. Brod</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L." last="Aldred">Jason L. Aldred</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22508376</idno><idno type="pmc">3707928</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707928</idno><idno type="RBID">PMC:3707928</idno><idno type="doi">10.1002/mds.24998</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000264</idno><idno type="wicri:Area/Pmc/Curation">000264</idno><idno type="wicri:Area/Pmc/Checkpoint">000212</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000D99</idno><idno type="wicri:Area/PubMed/Curation">000D99</idno><idno type="wicri:Area/PubMed/Checkpoint">000F39</idno><idno type="wicri:Area/Ncbi/Merge">003631</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S." last="Brod">Lissa S. Brod</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L." last="Aldred">Jason L. Aldred</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Antiparkinson Agents (administration & dosage)</term><term>Antiparkinson Agents (pharmacokinetics)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Area Under Curve</term><term>Carbidopa (administration & dosage)</term><term>Carbidopa (pharmacokinetics)</term><term>Carbidopa (therapeutic use)</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Area Under Curve</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P2">Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects.</p></sec><sec id="S2"><title>Methods</title><p id="P3">We compared 4-week outpatient treatments with carbidopa 75 mg and 450 mg/day administered with levodopa on the subjects’ normal schedule. After each treatment phase subjects had two 2-hour levodopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding four weeks and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and levodopa and carbidopa plasma concentrations were monitored during the infusions.</p></sec><sec id="S3"><title>Results</title><p id="P4">Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four levodopa infusions although AUC for plasma levodopa was modestly increased with 450 mg of carbidopa. Nine subjects reported the high carbidopa outpatient phase was associated with greater response to levodopa.</p></sec><sec id="S4"><title>Conclusion</title><p id="P5">Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day.</p></sec></div></front></TEI><double pmid="22508376"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S." last="Brod">Lissa S. Brod</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L." last="Aldred">Jason L. Aldred</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22508376</idno><idno type="pmc">3707928</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707928</idno><idno type="RBID">PMC:3707928</idno><idno type="doi">10.1002/mds.24998</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000264</idno><idno type="wicri:Area/Pmc/Curation">000264</idno><idno type="wicri:Area/Pmc/Checkpoint">000212</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S." last="Brod">Lissa S. Brod</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L." last="Aldred">Jason L. Aldred</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation><nlm:aff id="A1">Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center (PADRECC)</nlm:aff><wicri:noCountry code="subfield">Education and Clinical Center (PADRECC)</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Oregon Health & Science University</nlm:aff></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P2">Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects.</p></sec><sec id="S2"><title>Methods</title><p id="P3">We compared 4-week outpatient treatments with carbidopa 75 mg and 450 mg/day administered with levodopa on the subjects’ normal schedule. After each treatment phase subjects had two 2-hour levodopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding four weeks and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and levodopa and carbidopa plasma concentrations were monitored during the infusions.</p></sec><sec id="S3"><title>Results</title><p id="P4">Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four levodopa infusions although AUC for plasma levodopa was modestly increased with 450 mg of carbidopa. Nine subjects reported the high carbidopa outpatient phase was associated with greater response to levodopa.</p></sec><sec id="S4"><title>Conclusion</title><p id="P5">Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day.</p></sec></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease.</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S" last="Brod">Lissa S. Brod</name><affiliation wicri:level="2"><nlm:affiliation>Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, Oregon, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, Oregon</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L" last="Aldred">Jason L. Aldred</name></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G" last="Nutt">John G. Nutt</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="doi">10.1002/mds.24998</idno><idno type="RBID">pubmed:22508376</idno><idno type="pmid">22508376</idno><idno type="wicri:Area/PubMed/Corpus">000D99</idno><idno type="wicri:Area/PubMed/Curation">000D99</idno><idno type="wicri:Area/PubMed/Checkpoint">000F39</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease.</title><author><name sortKey="Brod, Lissa S" sort="Brod, Lissa S" uniqKey="Brod L" first="Lissa S" last="Brod">Lissa S. Brod</name><affiliation wicri:level="2"><nlm:affiliation>Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, Oregon, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Portland VA Medical Center Parkinson Disease Research, Education and Clinical Center, Portland, Oregon</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Aldred, Jason L" sort="Aldred, Jason L" uniqKey="Aldred J" first="Jason L" last="Aldred">Jason L. Aldred</name></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G" last="Nutt">John G. Nutt</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="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Antiparkinson Agents (administration & dosage)</term><term>Antiparkinson Agents (pharmacokinetics)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Area Under Curve</term><term>Carbidopa (administration & dosage)</term><term>Carbidopa (pharmacokinetics)</term><term>Carbidopa (therapeutic use)</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Area Under Curve</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Administration Schedule</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Treatment Outcome</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recommended doses of carbidopa are 75-200 mg/day. Higher doses could inhibit brain aromatic amino-acid decarboxylase and reduce clinical effects. We compared 4-week outpatient treatments with carbidopa (75 and 450 mg/day) administered with L-dopa on the subjects' normal schedule. After each treatment phase, subjects had two 2-hour L-dopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding 4 weeks, and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and L-dopa and carbidopa plasma concentrations were monitored during the infusions. Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high-carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four L-dopa infusions, although AUC for plasma L-dopa was modestly increased with 450 mg of carbidopa. Nine subjects reported that the high-carbidopa outpatient phase was associated with greater response to L-dopa. Doses of 450 mg/day of carbidopa did not reduce the responses to L-dopa infusion, extending the safe range of carbidopa to 450 mg/day.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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