THE INFLUENCE OF NET WATER-ABSORPTION ON THE PERMEABILITY OF ANTIPYRINE AND LEVODOPA IN THE HUMAN JEJUNUM

Food ingestion can influence the absorption of levodopa in the intesti ne and thereby contribute to fluctuations of motor functions in Parkin son patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route propos ed to be influenced by net transport of water across the intestinal ep ithelium, might occur for a small and hydrophilic drug such as levodop a. In the present study we studied how luminal L-leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorpt ion, and levodopa uptake in the human small intestine, since this poss ibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers t o study the effects of induced net fluid absorption on the small intes tinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorp tion was observed only when L-leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal perme ability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinson's disease cannot be explained by differences in transmucosal water flux in the human small intestin e.