The on-going quest for a long-acting oral form of levodopa

Levodopa is the gold standard symptomatic treatment for Parkinson's Disease (PD). However, its oral formulations lead to fluctuating plasma concentrations with delayed absorption in the stomach and low distribution in the brain due to its metabolism.

In this article, we first discuss the pharmacokinetics and pharmacodynamics of levodopa, exposing the problematics of the current levodopa formulations. We then discuss the more recent oral formulations designed to relieve these setbacks, including the development of controlled- and extended-release formulations. Finally, we expose the different alternative routes of administration that can be used, specifically in the case of patients with advanced PD.

With the progression of PD from early to advanced stages, levodopa doses must often be increased with concentrations that remain unstable, leading to sub-optimal symptomatic control and motor complications. Remedying this requires a shift in treatments from the classic oral formulations to more long-acting oral formulations or the use of different administration routes. Among these new administration routes, inhaled levodopa and continuous subcutaneous foslevodopa/foscarbidopa stand out as the most studied and less invasive options. However, with adverse effects associated with each solution, it is important to find approaches that are adapted to each patient.