This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonze, M. D. Articles by Money, S. R. Search for Related Content PubMed PubMed Citation Articles by Gonze, M. D. Articles by Money, S. R. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Blood Thinners Deep Vein Thrombosis Related Collections Animal models of human disease Anticoagulant mechanisms

(Circulation. 2000;101:2658.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Orally Administered Unfractionated Heparin With Carrier Agent Is Therapeutic for Deep Venous Thrombosis

Mark D. Gonze, MD; Khashayar Salartash, MD; W. Charles Sternbergh, III, MD; Robert A. Baughman, PhD; Andrea Leone-Bay, PhD; Samuel R. Money, MD

From the Department of Surgery, The Ochsner Medical Institutions, New Orleans, La (M.D.G., K.S., W.C.S., A.L.-B., S.R.M.), and Emisphere Technologies, Tarrytown, NY (R.A.B.).

Correspondence to Samuel R. Money, MD, Department of Surgery, 1516 Jefferson Hwy, New Orleans, LA 70121. E-mail smoney{at}ochsner.org

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).

Methods and 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.

Key Words: thrombosis • veins • heparin

This article has been cited by other articles:

				Y. Qi, G. Zhao, D. Liu, Z. Shriver, M. Sundaram, S. Sengupta, G. Venkataraman, R. Langer, and R. Sasisekharan Delivery of therapeutic levels of heparin and low-molecular-weight heparin through a pulmonary route PNAS, June 29, 2004; 101(26): 9867 - 9872. [Abstract] [Full Text] [PDF]

				B. H. Tonnessen and S. R. Money Low-Molecular-Weight Heparin Versus Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer Perspectives in Vascular Surgery and Endovascular Therapy, June 1, 2004; 16(2): 144 - 146. [Abstract] [PDF]

				F. G.P. Welt, T. C. Woods, and E. R. Edelman Oral Heparin Prevents Neointimal Hyperplasia After Arterial Injury: Inhibitory Potential Depends on Type of Vascular Injury Circulation, December 18, 2001; 104(25): 3121 - 3124. [Abstract] [Full Text] [PDF]

				D. S. Sumner Expert Commentary on Wakefield, T.W.: The Safety, Efficacy, and Cost Efficiency of Outpatient Treatment of Acute Deep Venous Thrombosis with Low Molecular Weight Heparin (pp. 19-26) Perspectives in Vascular Surgery and Endovascular Therapy, January 1, 2000; 13(2): 119 - 123. [PDF]