l-Dopa has been used for Parkinson’s disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using d-phenylglycine to guard l-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1). Methods: d-Phenylglycine was chemically attached on l-dopa to form d-phenylglycine-l-dopa as a dipeptide prodrug of l-dopa. The cross-membrane transport of this dipeptide and l-dopa via PepT1 was compared in brushboarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by in situ jejunal. | Wang et al. Journal of Biomedical Science 2010 17 71 http content 17 1 71 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Evidence of d-phenylglycine as delivering tool for improving l-dopa absorption 1 1 2 3 4 1 Chun-Li Wang Yang-Bin Fan Hsiao-Hwa Lu Tung-Hu Tsai Ming-Cheng Tsai Hui-Po Wang Abstract Background l-Dopa has been used for Parkinson s disease management for a long time. However its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using d-phenylglycine to guard l-dopa for better absorption in the intestine via intestinal peptide transporter I PepT1 . Methods d-Phenylglycine was chemically attached on l-dopa to form d-phenylglycine-l-dopa as a dipeptide prodrug of l-dopa. The cross-membrane transport of this dipeptide and l-dopa via PepT1 was compared in brushboarder membrane vesicle BBMV prepared from rat intestine. The intestinal absorption was compared by in situ jejunal perfusion in rats. The pharmacokinetics after . and . administration of both compounds were also compared in Wistar rats. The striatal dopamine released after . administration of d-phenylglycine-l-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with -methamphetamine MA . Results The BBMV uptake of d-phenylglycine-l-dopa was inhibited by Gly-Pro Gly-Phe and cephradine the typical PepT1 substrates but not by amino acids Phe or l-dopa. The cross-membrane permeability Pm determined in rat jejunal perfusion of d-phenylglycine-l-dopa was higher than that of l-dopa vs. . The oral bioavailability of d-phenylglycine-l-dopa was times higher than that of l-dopa in rats. A sustained .
