In-vitro interaction of L-dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability?

J Pharm Pharmacol. 2009 Oct;61(10):1303-7. doi: 10.1211/jpp/61.10.0005.

Abstract

Objectives: Recent investigations on the pharmacokinetics of levodopa (L-dopa) indicated that the presence of Helicobacter pylori in patients with Parkinson's disease, orally treated with L-dopa, influences the absorption of this compound, which consequently leads to decreased plasma levels. Therefore this work aims to study a potential in-vitro interaction of L-dopa with H. pylori and its surface adhesins.

Methods: Solutions containing L-dopa of different concentrations were incubated with H. pylori at different bacterial densities and time intervals. Free L-dopa was quantified from the incubation supernatants by HPLC. A flow cytometric assay with fluorescence labelled H. pylori was used to investigate the influence of L-dopa on the bacterial adhesion of H. pylori: FITC-labelled bacteria were pre-incubated with L-dopa, followed by incubation with gastric epithelial cells (AGS cells) and FACS quantification of adhering bacteria.

Key findings: Evaluation of time- and concentration-dependent incubation experiments indicated a significant decrease in L-dopa concentrations when coming into contact with H. pylori. The reduction in L-dopa concentrations was determined as 47 to 12%, referred to the initial starting concentration, with time-dependency and dependency of the H. pylori density. FITC-labelled H. pylori, pre-incubated with differing L-dopa concentrations, were shown to have a significantly reduced bacterial adhesion to AGS cells, with a maximum reduction of 22 +/- 9%. These results demonstrate a direct interaction of L-dopa with the outer membrane proteins of H. pylori responsible for the adhesion to gastric epithelial cells. By this interaction the unbound L-dopa concentration in bacterial suspension was strongly reduced.

Conclusions: This study suggests a potential in-vitro interaction of L-dopa with H. pylori adhesins, confirming the clinical changes found in pharmacokinetics of L-dopa therapy by H. pylori-positive patients with Parkinson's disease.

MeSH terms

  • Adhesins, Bacterial / adverse effects*
  • Bacterial Adhesion / drug effects
  • Biological Availability
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / microbiology
  • Helicobacter pylori / drug effects*
  • Humans
  • Levodopa / pharmacokinetics*
  • Time Factors

Substances

  • Adhesins, Bacterial
  • Levodopa