Pharmacokinetic‐pharmacodynamic crossover comparison of two levodopa extension strategies
Identifieur interne : 002136 ( Main/Exploration ); précédent : 002135; suivant : 002137Pharmacokinetic‐pharmacodynamic crossover comparison of two levodopa extension strategies
Auteurs : Peter A. Lewitt [États-Unis] ; Danna Jennings [États-Unis] ; Kelly E. Lyons [États-Unis] ; Rajesh Pahwa [États-Unis] ; Adrian L. Rabinowicz [États-Unis] ; James Wang [États-Unis] ; Maria Guarnieri [États-Unis] ; Jean P. Hubble [États-Unis] ; Harold Murck [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2009-07-15.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Aged, Analysis of Variance, Antiparkinson Agents (blood), Antiparkinson Agents (pharmacokinetics), Antiparkinson Agents (therapeutic use), Carbidopa (pharmacokinetics), Carbidopa (therapeutic use), Catechols (pharmacokinetics), Catechols (therapeutic use), Comparative study, Cross-Over Studies, Disability Evaluation, Dose-Response Relationship, Drug, Drug Delivery Systems (classification), Drug Delivery Systems (methods), Drug Therapy, Combination, Entacapone, Female, Fluctuations, Humans, Levodopa, Levodopa (blood), Levodopa (pharmacokinetics), Levodopa (therapeutic use), Male, Middle Aged, Nervous system diseases, Nitriles (pharmacokinetics), Nitriles (therapeutic use), Parkinson Disease (blood), Parkinson Disease (drug therapy), Parkinson disease, Parkinson's disease, Pharmacodynamics, Pharmacokinetics, Retrospective Studies, Severity of Illness Index, Strategy, Time Factors, entacapone, levodopa, motor fluctuation, pharmacodynamics, pharmacokinetics.
- MESH :
- chemical , blood : Antiparkinson Agents, Levodopa.
- chemical , pharmacokinetics : Antiparkinson Agents, Carbidopa, Catechols, Levodopa, Nitriles.
- chemical , therapeutic use : Antiparkinson Agents, Carbidopa, Catechols, Levodopa, Nitriles.
- blood : Parkinson Disease.
- classification : Drug Delivery Systems.
- drug therapy : Parkinson Disease.
- methods : Drug Delivery Systems.
- Aged, Analysis of Variance, Cross-Over Studies, Disability Evaluation, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Time Factors.
Abstract
Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L‐dopa pharmacokinetics (PK) and clinical effects after two doses of CL‐CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near‐equivalent mean L‐dopa area‐under‐the‐concentration‐curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL‐CR, P = 0.86). The mean hourly fluctuation index for L‐dopa concentration was 235% for CLE and 196% for CL‐CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL‐CR, 1,840 ± 889 (P = 0.33). During the PK studies, the mean time that L‐dopa concentration was ≥1,000 ng/mL for CLE was 291 ± 88 minutes and for CL‐CR, 306 ± 86 (P = 0.33). The mean percent‐time in “off” state was 18% for CLE and 28% for CL‐CR (P = 0.017), “on state without dyskinesia” was 64% for CLE and 65% for CL‐CR (P = 0.803), and “on state with nontroublesome dyskinesia” was 18% for CLE and 7% for CL‐CR (P = 0.03). Despite less “off” time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. © 2009 Movement Disorder Society
Url:
DOI: 10.1002/mds.22587
Affiliations:
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-07-15">2009-07-15</date><biblScope unit="vol">24</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1319">1319</biblScope><biblScope unit="page" to="1324">1324</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">CE60AC3975D087FFD56D71501497A712CEAED1D8</idno><idno type="DOI">10.1002/mds.22587</idno><idno type="ArticleID">MDS22587</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Analysis of Variance</term><term>Antiparkinson Agents (blood)</term><term>Antiparkinson Agents (pharmacokinetics)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Carbidopa (pharmacokinetics)</term><term>Carbidopa (therapeutic use)</term><term>Catechols (pharmacokinetics)</term><term>Catechols (therapeutic use)</term><term>Comparative study</term><term>Cross-Over Studies</term><term>Disability Evaluation</term><term>Dose-Response Relationship, Drug</term><term>Drug Delivery Systems (classification)</term><term>Drug Delivery Systems (methods)</term><term>Drug Therapy, Combination</term><term>Entacapone</term><term>Female</term><term>Fluctuations</term><term>Humans</term><term>Levodopa</term><term>Levodopa (blood)</term><term>Levodopa (pharmacokinetics)</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Nervous system diseases</term><term>Nitriles (pharmacokinetics)</term><term>Nitriles (therapeutic use)</term><term>Parkinson Disease (blood)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>Pharmacodynamics</term><term>Pharmacokinetics</term><term>Retrospective Studies</term><term>Severity of Illness Index</term><term>Strategy</term><term>Time Factors</term><term>entacapone</term><term>levodopa</term><term>motor fluctuation</term><term>pharmacodynamics</term><term>pharmacokinetics</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="pharmacokinetics" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Catechols</term><term>Levodopa</term><term>Nitriles</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Catechols</term><term>Levodopa</term><term>Nitriles</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Drug Delivery Systems</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>Drug Delivery Systems</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Analysis of Variance</term><term>Cross-Over Studies</term><term>Disability Evaluation</term><term>Dose-Response Relationship, Drug</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Retrospective Studies</term><term>Severity of Illness Index</term><term>Time Factors</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Entacapone</term><term>Etude comparative</term><term>Fluctuation</term><term>Lévodopa</term><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Pharmacocinétique</term><term>Pharmacodynamie</term><term>Stratégie</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Controlled‐release carbidopa and levodopa (CL‐CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L‐dopa) effects. In a randomized, open‐label crossover study of 17 PD subjects with wearing‐off responses, we compared 8‐hour L‐dopa pharmacokinetics (PK) and clinical effects after two doses of CL‐CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near‐equivalent mean L‐dopa area‐under‐the‐concentration‐curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL‐CR, P = 0.86). The mean hourly fluctuation index for L‐dopa concentration was 235% for CLE and 196% for CL‐CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 ± 760 ng/mL and for CL‐CR, 1,840 ± 889 (P = 0.33). During the PK studies, the mean time that L‐dopa concentration was ≥1,000 ng/mL for CLE was 291 ± 88 minutes and for CL‐CR, 306 ± 86 (P = 0.33). The mean percent‐time in “off” state was 18% for CLE and 28% for CL‐CR (P = 0.017), “on state without dyskinesia” was 64% for CLE and 65% for CL‐CR (P = 0.803), and “on state with nontroublesome dyskinesia” was 18% for CLE and 7% for CL‐CR (P = 0.03). Despite less “off” time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability. © 2009 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Kansas</li><li>Michigan</li><li>New Jersey</li></region></list><tree><country name="États-Unis"><region name="Michigan"><name sortKey="Lewitt, Peter A" sort="Lewitt, Peter A" uniqKey="Lewitt P" first="Peter A." last="Lewitt">Peter A. Lewitt</name></region><name sortKey="Guarnieri, Maria" sort="Guarnieri, Maria" uniqKey="Guarnieri M" first="Maria" last="Guarnieri">Maria Guarnieri</name><name sortKey="Hubble, Jean P" sort="Hubble, Jean P" uniqKey="Hubble J" first="Jean P." last="Hubble">Jean P. Hubble</name><name sortKey="Jennings, Danna" sort="Jennings, Danna" uniqKey="Jennings D" first="Danna" last="Jennings">Danna Jennings</name><name sortKey="Lyons, Kelly E" sort="Lyons, Kelly E" uniqKey="Lyons K" first="Kelly E." last="Lyons">Kelly E. Lyons</name><name sortKey="Murck, Harold" sort="Murck, Harold" uniqKey="Murck H" first="Harold" last="Murck">Harold Murck</name><name sortKey="Pahwa, Rajesh" sort="Pahwa, Rajesh" uniqKey="Pahwa R" first="Rajesh" last="Pahwa">Rajesh Pahwa</name><name sortKey="Rabinowicz, Adrian L" sort="Rabinowicz, Adrian L" uniqKey="Rabinowicz A" first="Adrian L." last="Rabinowicz">Adrian L. Rabinowicz</name><name sortKey="Wang, James" sort="Wang, James" uniqKey="Wang J" first="James" last="Wang">James Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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