Adjunction of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) to levodopa/carbidopa (LD/CD) improves motor symptoms in patients with Parkinson disease (PD) by a prolonged elimination of LD. But it is not known whether EN addition influences gastric emptying and thus LD pharmacokinetics and pharmacodynamics. Objectives were to simultaneously determine plasma LD elimination, gastric emptying, and clinical response after a single intake of the same LD dosage as LD/CD--or as (LD/CD/EN) formulation on 2 consecutive days. In both groups, PD patients with delayed gastric emptying had significant lower LD plasma concentrations. Addition of EN did not influence gastric emptying but significantly improved motor response, which was not different for patients with delayed gastric emptying. However, with and without EN adjunction gastric emptying distinctly contributes to the variability of plasma LD bioavailability. This may impact LD delivery to the brain and thus motor response in PD patients. Therefore, fine tuning of LD application, which considers gastric emptying, becomes more and more essential in advanced PD stages with a reduced striatal neuronal dopamine capacity, which is responsible for maintenance of motor response in early PD patients.

Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Objectives were to determine the clinical response after EN addition and the plasma degradation of LD and 3-O-methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson's disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t.i.d.) within a standardised setting. We scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed moments. Motor impairment significant better improved probably due to significant higher maximum concentrations [C(max)] and computed area under the curve values of LD levels during the LD/CD/EN condition. Time to C(max) of LD was significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3-OMD levels appeared. A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.

The short plasma half-life limits the antiparkinsonian efficacy of levodopa/carbidopa (LD/CD). Administration of LD/CD with the catechol-O-methyltransferase inhibitor entacapone in one tablet (LCE) may extend plasma half-life of LD and thus its effect on motor symptoms in patients with Parkinson's disease (PD). The objectives of this study were to monitor the motor response to a switch from LD/CD to LCE by a simultaneous performance of an instrumental motor test and rating of motor symptoms and to compare the LD plasma behavior between both conditions in terms of stability. Twenty-one treated PD patients received LD/CD and then the identical oral LD dosage of LCE within a standardized setting on 2 consecutive days. Rating better reflected the motor improvement after LD application than the instrumental test. Motor symptoms of PD patients decreased significantly more during the LCE than the LD/CD condition, probably due to significantly higher LD plasma levels and a significantly less pronounced fall of the LD concentrations following the second LD intake. Our study shows a more stable LD plasma behavior during LCE intake and accordingly a better effect on motor symptoms according to rating outcomes and motor test results to a lesser extent.