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

Objectives-Entacapone is a specific, potent, peripherally acting catechol-O -methyltransferase (COMT) inhibitor. It has been shown to improve the bioav ailability of plasma levodopa and extend its clinical effect when used as a n adjunct to standard levodopa preparations, but there is little experience of the effect of entacapone on controlled release levodopa preparations. Methods-A double blind, placebo controlled, single dose, randomised, cross over trial was performed in 14 patients with Parkinson's disease with motor fluctuations to investigate the clinical effect of a single dose of entaca pone (200 mg) when administered with either standard levodopa-carbidopa (Si nemet(TM)) or controlled release levodopa-carbidopa preparations (Sinemet C RTM). Results-When entacapone was administered with standard Sinemet(TM) the dura tion of the clinical response to standard Sinemet(TM) was longer in compari son with the response after placebo (p=0.02). Moreover, in the same patient s, entacapone significantly increased the duration of the clinical response to Sinemet CRTM (p=0.05) without prolonging the latency of response or enh ancing dyskinesias. Conclusions-These data confirm the clinical efficacy of entacapone-standard Sinemet(TM) combination. They also indicate that adding entacapone to cont rolled release levodopa preparations might provide a useful treatment optio n in patients with Parkinson's disease with motor fluctuations. A double bl ind clinical. trial with a chronically administered entacapone-Sinemet CRTM combination is, however, required to verify this viewpoint.