The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease

摘要

OBJECTIVES—Entacaponeis a specific, potent, peripherally actingcatechol-O-methyltransferase (COMT)inhibitor. It has been shown to improve the bioavailability of plasmalevodopa and extend its clinical effect when used as an adjunct tostandard levodopa preparations, but there is little experience of theeffect of entacapone on controlled release levodopa preparations.
METHODS—A doubleblind, placebo controlled, single dose, randomised, cross over trialwas performed in 14 patients with Parkinson's disease with motorfluctuations to investigate the clinical effect of a single dose ofentacapone (200 mg) when administered with either standardlevodopa-carbidopa (SinemetTM) or controlled release levodopa-carbidopapreparations (Sinemet CRTM).
RESULTS—Whenentacapone was administered with standard SinemetTM the duration of theclinical response to standard SinemetTM was longer in comparison withthe response after placebo (p=0.02). Moreover, in the same patients,entacapone significantly increased the duration of the clinicalresponse to Sinemet CRTM (p=0.05) without prolonging the latency ofresponse or enhancing dyskinesias.
CONCLUSIONS—These dataconfirm the clinical efficacy of entacapone-standard SinemetTMcombination. They also indicate that adding entacapone to controlledrelease levodopa preparations might provide a useful treatment optionin patients with Parkinson's disease with motor fluctuations. A doubleblind clinical trial with a chronically administered entacapone-SinemetCRTM combination is, however, required to verify this viewpoint.