Heparin absorption

During the past few decades, a number of important studies were published on the effect of cholic acid derivatives on the absorption of macromolecules [81]. Guarini and Ferrari [84—86] compared simultaneous oral dosing of NaDOC and heparin to pretreatment with NaDOC by oral gavage in dogs followed by oral heparin administration at a 0.5-24-h interval. In all pretreatment regimens, NaDOC enhanced heparin absorption, with the maximum effect observed when heparin was administered 1 h after NaDOC. 

Guarini, S., and W. Ferrari. 1984. Structural restriction in bile acids and non-ionic detergents for promotion of heparin absorption from rat gastro-intestinal tract. Arch Int Pharmacodyn Ther 271 4. 

Brayden D, Creed E, O Connell A, Leipold H, Argawal R, Leone-Bay A (1997) Heparin absorption across the intestine effects of sodium N-[8-(2-hydroxybenzoyl)amino]capry-late in rat in situ intestinal instillations and in Caco-2 monolayers. Pharm Res 14 1772-1779... 

Chromatographic methods (essentially using ion-exchange resins) are especially useful for separating heparin from other glycosaminoglycans, for further analytical and structural characterization. However, it should be realized that recovery of heparin from resins is seldom quantitative,42 probably because of irreversible absorption of heparin fractions in the... 

Schanker LS, Burton JA (1976) Absorption of heparin and cyanocobalamin from the rat lung. Proc Soc Exp Biol Med 152 377-380. 

Absorption/Distribution - Heparin is not adsorbed from the Gl tract. An IV bolus results in immediate anticoagulant effects. The duration of action is dose-dependent. Peak plasma levels of heparin are achieved 2 to 4 hours... 

Motlekar NA, Fasano A, Wachtel MS, Youan BB. Zonula occludens toxin synthetic derivative AT1002 enhances in vitro and in vivo intestinal absorption of low molecular weight heparin. J Drug Target 2006 14 321-9. 

Heparin is prescribed on a unit (lU) rather than milligram basis. Tlie dose must be determined on an individual basis. Heparin is not absorbed after oral administration and therefore must be given parenterally. Intravenous administration results in an almost immediate anticoagulant effect. There is an approximate 2-hour delay in onset of drug action after subcutaneous administration. Intramuscular injection of heparin is to be avoided because of unpredictable absorption rates, local bleeding, and irritation. Heparin is not bound to plasma proteins or secreted into breast mUk, and it does not cross the placenta. 

Maikov D, Wang HZ, Dinh S, Gomez-Orellana I. Pathway of oral absorption of heparin with sodium V-[8-(2-hydroxybenzoyl)amino] caprylate. Pharm Res 2002 19(8) 1180—1184. 

The data on protein adsorption as affected by immobilized heparin is quite contradictory. In Refs.114> and115), serum albumin was shown to be predominantly adsorbed by the HCP, whereas in the majority of other works the observed dependence was the opposite. Table 14 compiles the results of the studies of the absorption of plasma proteins by HCP of two different types 64). Such thrombogenic proteins as fibrinogen and thrombin are seen to be the ones adsorbed most. 

Plasma was separated from heparinized blood samples, ahquoted and stored at — 80°C. All samples were then analyzed simultaneously with identical hatches of antibodies and other reagents. ELISAs for the detection of sICAM-1, sE-selectin and IL-12 were performed with ELI-Pairs (Diaclone, France distributed by Holzel, Germany). 96-well Maxisorp plates (Nunc) were coated overnight with capture antibodies at 4°C. After 1 h sample incubation, detection was performed with biotinylated anti-ICAM-1, anti-sE-selectin or anti IL-12 detection antibodies followed by streptavidin-horse raddish peroxidase and a TMB color reaction. Light absorption was detected with a Spectra ELISA reader at 450 nm. 

In the late 1960s, Engel and coworkers [56-58] proposed sulfated and sulfonated surfactants as absorption promoters for two biological macromolecules, heparin and insulin. In these studies, sodium lauryl sulfate (SLS) promoted the absorption of heparin but not of insulin intraduodenally administered in rats and dogs. 

Leone-Bay, A., et al. 1998. Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin. J Med Chem 41 1163. 

Engel, R.H., and S.J. Riggi. 1969. Effect of sulfated and sulfonated surfactants on the intestinal absorption of heparin. Proc Soc Exp Biol Med 130 879. 

Touitou, E., M. Donbrow, and E. Azaz. 1978. New hydrophilic vehicle enabling rectal and vaginal absorption of insulin, heparin, phenol red and gentamicin. J Pharm Pharmacol 30 662. 

Rama Prasad, Y.V., et al. 2004. In situ intestinal absorption studies on low molecular weight heparin in rats using Labrasol as absorption enhancer. Int J Pharm 271 225. 

Mori, S., et al. 2004. Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats. Biol Pharm Bull 27 418. 

Ziv, E., et al. 1983. Bile salts facilitate the absorption of heparin from the intestine. Biochem Pharmacol 32 773. 

Miyake, M., et al. 1984. Rectal absorption of lysozyme and heparin in rabbits in the presence of non-surfactant adjuvants. Chem Pharm Bull 32 2020. 

Tokunaga, Y., S. Muranishi, and H. Sezaki. 1978. Enhanced intestinal permeability to macromolecules. I. Effect of monoolein-bile salts mixed micelles on the small intestinal absorption of heparin. J Pharmacobiodyn 1 28. 

---