+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers



Heparin absorption across the intestine: effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate in rat in situ intestinal instillations and in Caco-2 monolayers



Pharmaceutical Research 14(12): 1772-1779



The effects of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on heparin intestinal absorption were studied using rat in situ ileal and colonic instillations and Caco-2 monolayers. The flux of heparin was tested in the following groups: i) heparin alone, ii) heparin in the presence of SNAC, iii) heparin in the presence of propylene glycol (PG), and iv) heparin in the presence of SNAC and PG. Heparin absorption was measured by the APTT assay in the in situ models and by the anti-Factor Xa assay in Caco-2. SNAC and [3H]-SNAC fluxes were assessed by HPLC and by scintillation counting respectively. In the rat ileal and colonic in situ instillations SNAC (17-35 mg) promoted heparin absorption in the presence and absence of PG without damaging the tissue. PG alone did not alter heparin absorption in situ, but it amplified the effect of SNAC. In Caco-2, enhanced heparin fluxes were variable in the presence of non-cytotoxic concentrations of SNAC (< 10 mg/ml) and these effects could not be discriminated from those of PG. Papp values for SNAC alone were 2.2 x 10(-5) cm/s and 2.0 x 10(-5) cm/s in the mucosal-to-serosal and serosal-to-mucosal directions respectively, suggesting a substantial passive transcellular flux. Transport of SNAC was significantly reduced in the presence of heparin and/or PG, perhaps indicating physical association between the agents. SNAC augmented heparin absorption alone and in combination with PG in the rat in situ models without causing toxicity. Caco-2 had limitations for testing increased heparin absorption due to cytotoxic effects of high concentrations of SNAC and PG. However, SNAC itself was well absorbed across Caco-2 and its mechanism of permeation was determined.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046236474

Download citation: RISBibTeXText

PMID: 9453067


Related references

Heparin absorption across the intestine Effects of sodium N- aminocaprylate in rat in situ intestinal instillations and in Caco-2 monolayers. Pharmaceutical Research (New York) 14(12): 1772-1779, 1997

Heparin absorption across the intestine Effects of sodium N- aminocaprylate in Caco-2 monolayers and in rat in situ instillations. Pharmaceutical Research (New York) 14(11 Suppl. ): S222, 1997

Pathway of oral absorption of heparin with sodium N-[8-(2-hydroxybenzoyl)amino] caprylate. Pharmaceutical Research 19(8): 1180-1184, 2002

Impact of Sodium N -[8-(2-Hydroxybenzoyl)amino]-caprylate on Intestinal Permeability for Notoginsenoside R1 and Salvianolic Acids in Caco-2 Cells Transport and Rat Pharmacokinetics. Molecules 23(11):, 2018

Oral delivery of heparin in combination with sodium N-(8-(2-hydroxybenzoyl)amino)caprylate: Pharmacological considerations. Pharmaceutical Research (New York) 14(12): 1830-1834, 1997

Oral delivery of heparin in combination with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate: pharmacological considerations. Pharmaceutical Research 14(12): 1830-1834, 1997

Investigation of the enhancing mechanism of sodium N-[8-(2-hydroxybenzoyl)amino]caprylate effect on the intestinal permeability of polar molecules utilizing a voltage clamp method. European Journal of Pharmaceutical Sciences 25(2-3): 307-312, 2005

Heparin oligosaccharides intestinal absorption using several absorption enhancers in Caco-2 cell monolayers. Fibrinolysis & Proteolysis 14(Suppl. 1): 50, 2000

Toxicological and absorption enhancing effects of glycofurol 75 and sodium glycocholate in monolayers of human intestinal epithelial (Caco-2) cells. International Journal of Pharmaceutics 95(1-3): 209-217, 1993

Effects of a new lipid-based drug delivery system on the absorption of low molecular weight heparin (Fragmin) through monolayers of human intestinal epithelial Caco-2 cells and after rectal administration to rabbits. European Journal of Pharmaceutical Sciences 1(6): 297-305, 1994

Paracellular absorption enhancement in intestinal Caco-2 monolayers by sodium caprate. European Journal of Pharmaceutical Sciences 2(1-2): 131, 1994

Phase I clinical study to select a novel oral formulation for ibandronate containing the excipient sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC). Die Pharmazie 67(3): 233-241, 2012

Assessment and modulation of acamprosate intestinal absorption: comparative studies using in situ, in vitro (CACO-2 cell monolayers) and in vivo models. European Journal of Pharmaceutical Sciences 22(5): 347-356, 2004

The role of the proton electrochemical gradient in the transepithelial absorption of amino acids by human intestinal Caco-2 cell monolayers. Journal of Membrane Biology 145(3): 245-256, 1995

Absorption enhancement in intestinal Caco-2 monolayers by sodium caprate Assessment of molecular weight dependence and visualisation of transport routes. Pharmaceutical Research (New York) 11(10 Suppl. ): S248, 1994