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

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.