Levodopa/carbidopa/entacapone in Parkinson’s disease

Abstract

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.

Keywords::

• anti-Parkinson’s agents/therapeutic use
• carbidopa
• catechol-O-methyl transferase inhibitor
• catechols/therapeutic use
• COMT inhibitor/pharmacodynamics
• COMT inhibitor/pharmacokinetics
• entacapone
• levodopa
• motor complications
• Parkinson diseases
• pharmacology
• Stavelo^®
• treatment

Financial & competing interests disclosure

L Seeberger has served as a consultant and advisor to Teva Neurosciences. RA Hauser has received Honoraria from the following pharmaceutical companies for consulting, advisory or speaking services during June 2008 to June 2009: Allergan Neuroscience, AlphMedica, ApotheCom, Axis Health Care, Bayer-Shering, Boehringer Ingelheim, CNS Schering Plough, Centopharm, Embryon, Eisai, Genzyme, GlaxoSmithKline, Impax, Ipsen Pharmaceuticals (formerly Vernalis), Kyowa Pharmaceutical, Merck, Novartis, Ortho McNeil, Pfizer, Prestwick, Quintiles, Santhera, Schwarz Pharma, Schering Plough, Solvay, Teva Neuroscience, Valeant, Vernalis (now Ipsen Pharmaceuticals). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.