Levodopa is the most efficacious agent for the treatment of motor features of 
Parkinson's disease but its chronic use is associated with the development of 
motor complications. Mounting evidence indicates the short half-life of levodopa 
and resultant pulsatile stimulation of striatal dopamine receptors leads to 
wearing off, motor fluctuations and dyskinesias. Longer acting dopaminergic 
agents, such as dopamine agonists, are less likely to cause motor fluctuations 
and dyskinesias but are not as efficacious for control of motor symptoms. 
Therefore, there is interest in exploring ways to deliver levodopa in a more 
continuous fashion, in an effort to maintain benefit through the day and reduce 
the development of motor fluctuations and dyskinesias. A dopa decarboxylase 
inhibitor (DDCI), such as carbidopa or benserazide, is administered with 
levodopa to attenuate its peripheral conversion to dopamine, reduce nausea and 
increase central bioavailability. When levodopa is administered with a DDCI, its 
main route of peripheral metabolism is via catechol-O-methyl transferase (COMT). 
A COMT inhibitor can be added to the combination of levodopa and a DDCI to 
further extend the levodopa peripheral half-life and increase central 
bioavailability. Stalevo is a combination tablet comprised of levodopa, 
carbidopa, and the COMT inhibitor entacapone. It is available in fixed-dose 
combinations of levodopa/carbidopa/entacapone, 50/12.5/200, 75/18.75/200, 
100/25/200, 125/31.25/200, 150/37.5/200 and 200/50/200 mg. Stalevo is currently 
approved for use in Parkinson's disease patients with end-of-dose wearing off.