Comparison of intestinal permeability and p‐glycoprotein effects on the intestinal absorption of enantiomers of 2‐(2‐hydroxypropanamido) benzoic acid in rats. Issue 1 (19th December 2016)

• Record Type: Journal Article
• Authors: Zhang, Qili; Zhang, Meiyan; Wang, Danlin; Zhao, Yunli; Yu, Zhiguo
• Is Part Of: Chirality. Volume 29:Issue 1(2017)
• Page Start: 26
• Page End: 32
• Publication Date: 2016-12-19
• Subjects: absorption rate coefficients (Ka) -- chirality -- comparison -- permeability values (Peff), molecular docking -- single‐pass intestinal perfusion (SPIP); Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22662
• Languages: English
• ISSNs: 0899-0042

Abstract

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 ( 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. Abstract :