Genetic polymorphism of catechol‐O‐methyltransferase and levodopa pharmacokinetic–pharmacodynamic pattern in patients with Parkinson's disease
Identifieur interne : 003908 ( Main/Exploration ); précédent : 003907; suivant : 003909Genetic polymorphism of catechol‐O‐methyltransferase and levodopa pharmacokinetic–pharmacodynamic pattern in patients with Parkinson's disease
Auteurs : Manuela Contin [Italie] ; Paolo Martinelli [Italie] ; Mirella Mochi [Italie] ; Roberto Riva [Italie] ; Fiorenzo Albani [Italie] ; Agostino Baruzzi [Italie]Source :
- Movement Disorders [ 0885-3185 ] ; 2005-06.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Aged, Analysis of Variance, Antiparkinson Agents (pharmacokinetics), Antiparkinson Agents (therapeutic use), Area Under Curve, Benserazide (therapeutic use), COMT polymorphism, Catechol O-Methyltransferase (genetics), Catechol O-methyltransferase, Drug Interactions, Female, Genotype, Human, Humans, Levodopa, Levodopa (blood), Levodopa (pharmacokinetics), Levodopa (therapeutic use), Male, Middle Aged, Motor Activity (drug effects), Nervous system diseases, Parkinson Disease (drug therapy), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson disease, Parkinson's disease, Pharmacogenetics, Pharmacokinetics, Polymorphism, Polymorphism, Genetic, Reaction Time (drug effects), levodopa, pharmacodynamics, pharmacokinetics.
- MESH :
- chemical , blood : Levodopa.
- chemical , genetics : Catechol O-Methyltransferase.
- chemical , pharmacokinetics : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Benserazide, Levodopa.
- drug effects : Motor Activity, Reaction Time.
- drug therapy : Parkinson Disease.
- genetics : Parkinson Disease.
- metabolism : Parkinson Disease.
- Aged, Analysis of Variance, Area Under Curve, Drug Interactions, Female, Genotype, Humans, Male, Middle Aged, Pharmacogenetics, Polymorphism, Genetic.
Abstract
We explored the potential effect of catechol‐O‐methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson's disease (PD). We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger‐tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half‐life, and the area under the plasma concentration–time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect–time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low‐activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate‐activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high‐activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic–pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic–pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society
Url:
DOI: 10.1002/mds.20410
Affiliations:
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We prospectively collected blood samples for COMT genotyping from a population of 104 PD patients. Each patient was examined by a standard oral levodopa/benserazide test, based on simultaneous serial measurements of plasma levodopa concentrations, finger‐tapping motor effects and dyskinesia ratings, up to 4 hours after dosing. The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration, plasma elimination half‐life, and the area under the plasma concentration–time curve. The main outcome levodopa pharmacodynamic variables were latency, duration, and magnitude of the motor effect elicited by the levodopa test dose, the area under the tapping effect–time curve, and the presence of dyskinesias. Nineteen patients (18%) harbored the low‐activity homozygous COMT genotype (A/A), 63 patients (61%) carried the intermediate‐activity heterozygous COMT genotype (A/G) and 22 patients (21%) had the high‐activity homozygous COMT genotype (G/G). The three groups were comparable for vital and clinical characteristics. No significant difference was found in levodopa main pharmacokinetic–pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients. We failed to identify clinically relevant levodopa pharmacokinetic–pharmacodynamic response patterns associated with the COMT polymorphism in PD patients. © 2005 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Italie</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Contin, Manuela" sort="Contin, Manuela" uniqKey="Contin M" first="Manuela" last="Contin">Manuela Contin</name></noRegion><name sortKey="Albani, Fiorenzo" sort="Albani, Fiorenzo" uniqKey="Albani F" first="Fiorenzo" last="Albani">Fiorenzo Albani</name><name sortKey="Baruzzi, Agostino" sort="Baruzzi, Agostino" uniqKey="Baruzzi A" first="Agostino" last="Baruzzi">Agostino Baruzzi</name><name sortKey="Martinelli, Paolo" sort="Martinelli, Paolo" uniqKey="Martinelli P" first="Paolo" last="Martinelli">Paolo Martinelli</name><name sortKey="Mochi, Mirella" sort="Mochi, Mirella" uniqKey="Mochi M" first="Mirella" last="Mochi">Mirella Mochi</name><name sortKey="Riva, Roberto" sort="Riva, Roberto" uniqKey="Riva R" first="Roberto" last="Riva">Roberto Riva</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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