Orally active heparin and low-molecular-weight heparin.
The heparins, (unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH)) given by subcutaneous or intravenous injection have been used extensively in the prevention and treatment of both venous and arterial thromboembolic disorders. The increasing use of the heparins, LMWHs in particular, in the out of hospital setting has stimulated interest in the development of orally absorbable antithrombotic agents that require little or no monitoring, and this includes the heparins. UFH or LMWH delivered orally has been shown to have an antithrombotic effect in animal thrombosis models although there is little change in plasma coagulation tests. The addition of a simple organic chemical N -(8-(2-hydroxybenzoyl)amino)caprylate (SNAC) to UFH markedly enhances its absorption. A phase II study in patients undergoing total hip replacement indicated that SNAC heparin in two different doses was as effective and safe as UFH given subcutaneously. A phase III clinical trial comparing two doses of SNAC heparin given orally with LMWH by subcutaneous injection for the prevention of venous thromboembolism in patients undergoing total hip replacement is currently underway.
Pineo
G F
GF
Thrombosis Research Unit, Foothills Hospital, University of Calgary, 1403 29th Street NW, Calgary, Alberta T2N 2T9, Canada. pineo@ucalgary.ca
Hull
R D
RD
Marder
V J
VJ
D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D002210:Caprylates / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007408:Intestinal Absorption; D015201:Meta-Analysis as Topic; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D002210:Caprylates; D006495:Heparin, Low-Molecular-Weight; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D006493:Heparin