Genetic polymorphism of catechol-O-methyltransferase and levodopa pharmacokinetic-pharmacodynamic pattern in patients with Parkinson's disease.
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.
Contin
Manuela
M
Neurology Clinic, Department of Neurological Sciences, University of Bologna, Via Foscolo 7, 40123 Bologna, Italy. manuela.contin@unibo.it
Martinelli
Paolo
P
Mochi
Mirella
M
Riva
Roberto
R
Albani
Fiorenzo
F
Baruzzi
Agostino
A
D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001545:Benserazide / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004347:Drug Interactions; D005260:Female; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011930:Reaction Time / Q000187:drug effects
D000978:Antiparkinson Agents; D007980:Levodopa; D001545:Benserazide; D002394:Catechol O-Methyltransferase