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

Expert Opin Pharmacother. 2018 Jun;19(9):1003-1011. doi: 10.1080/14656566.2018.1484108. Epub 2018 Jun 18.

Abstract

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.

Keywords: Levodopa; homocysteine; motor complications; neuronal repair; oxidative stress.

Publication types

  • Review

MeSH terms

  • Antioxidants / metabolism
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / therapeutic use*
  • Aromatic Amino Acid Decarboxylase Inhibitors / pharmacokinetics
  • Aromatic Amino Acid Decarboxylase Inhibitors / therapeutic use
  • Brain / metabolism
  • Catechol O-Methyltransferase Inhibitors / pharmacokinetics
  • Catechol O-Methyltransferase Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Levodopa / adverse effects
  • Levodopa / pharmacokinetics
  • Levodopa / therapeutic use*
  • Oxidative Stress
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology

Substances

  • Antioxidants
  • Antiparkinson Agents
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Catechol O-Methyltransferase Inhibitors
  • Levodopa