Comparison of intestinal permeability and p-glycoprotein effects on the intestinal absorption of enantiomers of 2-(2-hydroxypropanamido) benzoic acid in rats.

Abstract

The purpose of this study was to compare intestinal permeability between enantiomers of 2-(2-hydroxypropanamido) benzoic acid ((R)-/(S)-HPABA), a marine-derived antiinflammatory drug, using an in situ single-pass intestinal perfusion (SPIP) model in rats. Concentrations, isolated regions of small intestine, and p-glycoprotein (P-gp) inhibitor were performed to investigate their influences on the intestinal absorption of (R)-/(S)-HPABA. In addition, a molecular docking method was performed to illustrate our prediction. The absorption rate coefficients (Ka ) and permeability values (Peff ) of (R)-/(S)-HPABA were calculated. The permeability of (S)-HPABA was significantly (P<0.01) higher than that of (R)-HPABA in jejunum, and ileum permeability of (R)-/(S)-HPABA appeared best in ileum; the investigated concentrations ranged from 20 to 80μg/mL, Ka and Peff values of (R)-/(S)-HPABA increased linearly; in the presence of P-gp inhibitor (verapamil), Peff values of two enantiomers were increased significantly; and the effect of P-gp on absorption of (R)-HPABA is stronger than that of (S)-HPABA in ileum segment. Based on these results, carrier-mediated transport or passive transport combined with carrier-mediated transport seems to be the mechanism for intestinal absorption of (R)-/(S)-HPABA, and (R)-/(S)-HPABA may be recognized as the P-gp substrate. In addition, the intestinal permeability of (S)-HPABA is higher than that of (R)-HPABA.