Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets

Clin Neuropharmacol. May-Jun 2003;26(3):156-63. doi: 10.1097/00002826-200305000-00010.

Abstract

Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / blood
  • Antiparkinson Agents / pharmacokinetics*
  • Carbidopa / administration & dosage
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Drug Combinations
  • Duodenum
  • Female
  • Humans
  • Infusions, Parenteral
  • Levodopa / administration & dosage*
  • Levodopa / blood
  • Levodopa / pharmacokinetics*
  • Male
  • Middle Aged
  • Parkinson Disease / blood
  • Parkinson Disease / drug therapy*
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Drug Combinations
  • Levodopa
  • Carbidopa