The catechol-O-methyltransferase (COMT) inhibitor entacapone enhances the pharmacokinetic and clinical response to Sinemet CR in Parkinson's disease.
OBJECTIVE
Entacapone is a specific, potent, peripherally acting catechol-O-methyltransferase (COMT) inhibitor. It has been shown to improve the bioavailability of plasma levodopa and extend its clinical effect when used as an 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 entacapone (200 mg) when administered with either standard levodopa-carbidopa (Sinemet) or controlled release levodopa-carbidopa preparations (Sinemet CR).


RESULTS
When entacapone was administered with standard Sinemet the duration of the clinical response to standard Sinemet was longer in comparison with the response after placebo (p=0.02). Moreover, in the same patients, entacapone significantly increased the duration of the clinical response to Sinemet CR (p=0.05) without prolonging the latency of response or enhancing dyskinesias.


CONCLUSIONS
These data confirm the clinical efficacy of entacapone-standard Sinemet combination. They also indicate that adding entacapone to controlled release levodopa preparations might provide a useful treatment option in patients with Parkinson's disease with motor fluctuations. A double blind clinical trial with a chronically administered entacapone-Sinemet CR combination is, however, required to verify this viewpoint.
Piccini
P
P
Department of Neurology, Imperial College, School of Medicine, Hammersmith Hospital, London, UK. paola.piccini@csc.mrc.ac.uk
Brooks
D J
DJ
Korpela
K
K
Pavese
N
N
Karlsson
M
M
Gordin
A
A
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002230:Carbidopa / Q000493:pharmacokinetics*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009570:Nitriles; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; C071192:entacapone; D002230:Carbidopa