Optimizing levodopa therapy to treat wearing-off symptoms in Parkinson’s disease: focus on levodopa/carbidopa/entacapone

Abstract

Levodopa has been the mainstay of Parkinson’s disease (PD) therapy for over 40 years, with its efficacy surpassing that of other antiparkinsonian medications. As such, most PD patients eventually require levodopa-based therapy during the course of the disease. However, despite its proven efficacy, long-term levodopa therapy is associated with motor complications, with wearing-off being the most prevalent. Wearing-off occurs, in part, as a result of the short half-life of levodopa, which leads to fluctuations in plasma levodopa levels. A pharmacokinetic profile characterized by a higher trough value of levodopa can be achieved by combining levodopa/carbidopa with entacapone, which inhibits the peripheral breakdown of levodopa, resulting in higher plasma levodopa levels. Here, we review the limitations of conventional levodopa and the clinical data for levodopa/carbidopa/entacapone in treating patients with wearing-off.

Keywords::

• entacapone
• levodopa
• levodopa/carbidopa/entacapone
• motor fluctuations
• Parkinson’s disease
• wearing-off

Financial & competing interests disclosure

H Reichmann has acted on advisory boards, given lectures and received research grants from Bayer Health Care, Boehringer/Ingelheim, Cephalon, Desitin, GSK, Merck-Serono, Novartis, Orion, Pfizer, TEVA/Lundbeck, UCB Schwarz Pharma and Valeant. M Emre has served on advisory boards, received study grants or honoraria for being a speaker from Boehringer Ingelheim, Eisai, Novartis, Lundbeck and Orion. 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.

Writing assistance was utilized in the production of this manuscript. The authors thank Nadia Hashash, PhD, Medicus International for providing editorial assistance. Editorial assistance was funded by Novartis Pharmaceuticals and Orion Pharma.