Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients.

摘要

The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson's disease (PD) patients. Twelve PD patients experiencing "end-of-dose" type motor fluctuations were evaluated in this single-blind, randomized cross-over study. A single dose of either entacapone (200 mg) or placebo was co-administered with controlled release levodopa. Blood samples were taken every 30 minutes for 3 hours, and in 6 patients, sampling was continued for a further 3 hours. The clinical response to treatment was evaluated using the Unified Parkinson's Disease Rating Scale motor score. Addition of entacapone to levodopa treatment prolonged the "on" phase of the PD patients by 37% (p<0.05). This increased duration of 'on' time was concomitant with a significant increase in levodopa bioavailability (AUC). These data confirm the ability of entacapone to enhance the clinical efficacy of controlled release levodopa formulations, and provide further evidence that entacapone is of value in extending the benefits of levodopa in PD patients experiencing motor fluctuations.