No correlation between COMT genotype and entacapone benefits in Parkinson's disease

Abstract

Catechol-O-methyltransferase (COMT) inhibitors are used to increase the bioavailability of therapeutic L-dopa. We examined the efficacy of entacapone in Parkinson's disease patients who had daily "off" duration of <= 2 hours, and carried different COMT polymorphisms. A total of 168 PD patients were recruited from 19 centers. Subjects were administered with 100-200 mg of entacapone in combination with each dose of L-dopa for 2 months. The clinical efficacy was evaluated based on the activities of daily living (ADL), score on the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) stage, and Clinical Global Impression (CGI). COMT polymorphisms were genotyped. 3-O-methyldopa (3-OMD) levels were measured before and after the administration of entacapone. Entacapone administration produced significant improvements in the total daily "on" duration, ADL, UPDRS score, and H&Y stage. Nineteen patients (11.3%) had the low-activity COMT genotype, 68 patients (40.5%) had the intermediate-activity COMT genotype, and 81patients (48.2%) had the high-activity COMT genotype. The efficacy, and adverse effects of entacapone therapy did not differ between the three groups. There was a significant reduction in 3-OMD, but this did not differ among the three genotypes. Entacapone provided an increased "on" duration and improved motor function in all COMT genotypes.