Oral heparin: status review

Abstract

Unfractionated heparin and low molecular weight heparin are the most commonly used antithrombotic and thromboprophylactic agents in hospital practice. Extended out-of-hospital treatment is inconvenient in that these agents must be administered parenterally. Current research is directed at development of a safe and effective oral antithrombotic agent as an alternative for the effective, yet difficult to use vitamin K antagonists. A novel drug delivery technology that facilitates transport of drugs across the gastrointestinal epithelium has been harnessed to develop an oral dosage form of unfractionated heparin. Combining unfractionated heparin with the carrier molecule, sodium N-(8 [2-hydroxybenzoyl]amino) caprylate, or SNAC has markedly increased the gastrointestinal absorption of this drug. Preclinical and clinical studies to-date suggests that oral heparin-SNAC can confer a clinical efficacious effect; further confirmation is sought in planned clinical trials.

Figure 1

Schematic depiction of drug delivery technology. Carrier molecule (delivery agent) associates with drug molecule to create a transportable complex (lipophilic). Because of the weak association, carrier and drug dissociate by simple dilution on entering the blood circulation.

Figure 2

Anti-Factor Xa levels. Blood levels of Anti-Factor Xa after oral administration of heparin/SNAC in solution to healthy male volunteers (mean ± SEM). A dose response was observed. Heparin alone was not absorbed.

Figure 3

Anti-Factor Xa levels following oral administration of heparin/SNAC in hard-gelatin capsules. The study was done on healthy male volunteers (mean ± SD, n = 10, crossover study). Therapeutic levels were attained. Prophylactic levels of anti-factor Xa were only slightly elevated.