title: 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 80 μg/mL, Kaand Peffvalues of (R)-/(S)-HPABA increased linearly; in the presence of P-gp inhibitor (verapamil), Peffvalues 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.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Qili
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Danlin
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People's Republic of China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010539:Permeability; D051381:Rats; D013237:Stereoisomerism
chemical_list: C000594866:2-(2-hydroxypropanamido)benzoic acid; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001565:Benzoates
keywords: absorption rate coefficients (Ka); chirality; comparison; permeability values (Peff), molecular docking; single-pass intestinal perfusion (SPIP)