Long-term management of Parkinson's disease using levodopa combinations.

Introduction: Parkinson's disease is a chronic, neurodegenerative disease. Its symptoms and course are heterogeneous. After several years of investigative drug studies, levodopa remains the most efficacious drug despite its long-term limitations. Consequently, research into new drug delivery modes is ongoing.

Areas Covered: This review summarizes past and current advances of levodopa therapy with a focus on long-term patient management. Current research aims to increase drug bioavailability and to deliver it to the brain continuously. Reduced fluctuations improve drug efficacy and levodopa-associated motor complications. Less considered metabolic long-term consequences of levodopa are impaired methylation capacity and antioxidant defense. Both may contribute to disease progression and weaken physiological available human neuronal repair mechanisms.

Expert Opinion: New developed formulations will improve pharmacokinetic and pharmacodynamic behavior. The authors suggest the regular supplementation with methyl group-donating and free radical scavenging substrates to weaken the metabolic consequences of chronic and high levodopa dosing. Many patients perform this nutrient supplementation in their diet already.