The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on-off fluctuations

Br J Clin Pharmacol. 1986 Oct;22(4):429-36. doi: 10.1111/j.1365-2125.1986.tb02913.x.


We have studied the clinical effects and pharmacokinetics of levodopa infusions and oral therapy in seven patients with Parkinson's disease. They all showed on-off fluctuations whilst receiving long-term treatment with levodopa in combination with a peripheral decarboxylase inhibitor. Intravenous infusion at a constant rate for up to 16 h resulted in a smoother clinical response, and maintained plasma levodopa concentrations within narrower limits compared with conventional oral therapy. Following infusion rates of 32-80 mg h-1 (0.5-1.3 mg kg-1 h-1) the plasma concentration associated with optimum therapeutic response lay between 0.3 and 1.6 mg l-1. There was considerable variation in the oral absorption and elimination of levodopa, both within and between subjects. The concentration of 3-OMe dopa in plasma hardly increased during each day's levodopa therapy. In all cases levels were greater than the maximum concentrations of levodopa, sometimes by as much as a factor of 10. In contrast to most previous reports on the pharmacokinetics of levodopa, the data presented here are consistent with a two-compartment kinetic model. It is not known whether the difference in pharmacokinetics is due to chronic therapy or whether it is specific to those patients who show on-off phenomena, but such changes might be related in some way to the development of fluctuations in clinical response.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Carboxy-Lyases / antagonists & inhibitors
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Kinetics
  • Levodopa / administration & dosage
  • Levodopa / metabolism*
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism*
  • Random Allocation
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Tyrosine
  • Levodopa
  • Carboxy-Lyases
  • 3-methoxytyrosine