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

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 ( K a ) and permeability values ( P eff ) 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 80 μg/mL, K a and P eff values of ( R ) ‐/ ( S ) ‐ HPABA increased linearly; in the presence of P‐gp inhibitor (verapamil), P eff 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.