title: Orally administered unfractionated heparin with carrier agent is therapeutic for deep venous thrombosis.
abstract: BACKGROUND
  Orally administered heparin (OHEP) is unreliable because of poor absorption. Sodium N-(8[2-hydroxybenzoyl]amino) caprylate (SNAC) is an amido acid that facilitates the gastrointestinal absorption of heparin. We evaluated the effectiveness of OHEP combined with SNAC (OHEP/SNAC) in the treatment of deep-vein thrombosis (DVT).
  
  
  RESULTS
  An internal jugular DVT was produced in 54 male Sprague-Dawley rats. Animals were assigned to 6 different groups for 7 days of treatment: untreated control, subcutaneous heparin (SC HEP) (300 U/kg SC TID), SNAC only (300 mg/kg PO TID), OHEP only (30 mg/kg PO TID), low-molecular-weight heparin (LMWH) (enoxaparin 5 mg/kg SC QD), and OHEP/SNAC (30 mg/kg:300 mg/kg PO TID). The activated partial thromboplastin time (aPTT) and anti-factor X (anti-Xa) levels were measured. The incidence of residual DVT after 1 week of treatment was 100% (9 of 9) in the control group versus 10% (1 of 10) in the OHEP/SNAC and 10% (1 of 10) in the LMWH groups (P<0.001). There was also a significant reduction in clot weights between these groups. Compared with controls, there were no significant differences in the residual DVT in the SNAC-only (6 of 6), OHEP-only (9 of 9), or SC HEP (8 of 10) groups. Combination OHEP/SNAC was as effective in the resolution of the clot and reducing clot weight as LMWH. The aPTT levels in the OHEP/SNAC group peaked at 30 minutes and were significantly higher than in all other groups (P<0.01). Anti-Xa levels were elevated at 15 minutes after dosing in the OHEP/SNAC group and remained significantly elevated at 4 hours (P<0.001).
  
  
  CONCLUSIONS
  OHEP combined with a novel carrier agent (SNAC) successfully treated DVT in this rat model.
authors.affiliation: Department of Surgery, The Ochsner Medical Institutions, New Orleans, LA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Gonze
authors.forename: K
authors.initials: K
authors.lastname: Salartash
authors.forename: W C
authors.initials: WC
authors.lastname: Sternbergh
authors.forename: R A
authors.initials: RA
authors.lastname: Baughman
authors.forename: A
authors.initials: A
authors.lastname: Leone-Bay
authors.forename: S R
authors.initials: SR
authors.lastname: Money
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics*; D002210:Caprylates / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000493:pharmacokinetics*; D017984:Enoxaparin / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007601:Jugular Veins; D008297:Male; D010314:Partial Thromboplastin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D002210:Caprylates; D004337:Drug Carriers; D017984:Enoxaparin; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate