Genetic polymorphism of catechol-O-methyltransferase and levodopa pharmacokinetic-pharmacodynamic pattern in patient with parkinson's disease

Manuela Contin, Paolo Martinelli, Mirella Mochi, Roberto Riva, Fiorenzo Albani, Agostino Baruzzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)734-739
Number of pages6
JournalMovement Disorders
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2005

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Keywords

  • COMT polymorphism
  • Levodopa
  • Parkinson's disease
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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