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Comparison of intestinal permeability and p ‐glycoprotein effects on the intestinal absorption of enantiomers of 2‐(2‐hydroxypropanamido) benzoic acid in rats
Author(s) -
Zhang Qili,
Zhang Meiyan,
Wang Danlin,
Zhao Yunli,
Yu Zhiguo
Publication year - 2017
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22662
Subject(s) - chemistry , ileum , jejunum , passive transport , p glycoprotein , enantiomer , intestinal permeability , verapamil , permeability (electromagnetism) , biopharmaceutics classification system , pharmacology , absorption (acoustics) , chromatography , medicine , stereochemistry , biochemistry , solubility , organic chemistry , antibiotics , physics , membrane , multiple drug resistance , acoustics , calcium
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.