Novel Approaches to Optimization of Levodopa Therapy for Parkinson's Disease.

Levodopa (LD) is the most effective medication to treat Parkinson's disease (PD). However, motor fluctuations and drug-induced dyskinesia compromise the long-term success of levodopa therapy in PD. These response complications are due, at least in part, to fluctuating LD plasma levels (as a result of erratic gastric emptying, variable jejunal absorption, and most importantly, the short half-life of LD) with standard levodopa formulations. Keeping levodopa concentrations as constant as possible is the target for improving the pharmacokinetics and developing new ways of LD administration. In this article, we review novel oral and non-oral LD formulations including the ones that have successfully completed phase 3 clinical trials and have come to market and ones that are still in earlier phases of clinical development.