Oral heparin: status review

The current use of anticoagulants is extensive and it is estimated that 0.7% of the population in the Western world receive these drugs [1]. Broader indications for anticoagulants and their increased use in the outpatient settings as well as for long-term dosing has stimulated renewed interest in developing oral anticoagulant and antithrombotic agents. At present, the cornerstone of oral anticoagulants are the vitamin K antagonists, of which the coumarin derivative warfarin, (Coumadin) is the most widely used. It has been used clinically for more than 50 years, and has consistently demonstrated that adequate dosing virtually eliminates recurrent venous thrombosis [2,3]. Nevertheless, warfarin has serious drawbacks that require steady vigilance on the part of clinicians. These drawbacks include significant drug-drug and food-drug interactions, a slow onset and offset of effect, and a narrow therapeutic index. Because of the inherent variability in response over time and the consequently unpredictable pharmacodynamics of the drug, frequent monitoring is necessary, an inconvenience for the large number of patients who take it chronically. Even with optimal warfarin monitoring in patients with atrial fibrillation (AF), therapeutic anticoagulation is achieved only half the time [4,5]. Because of this, it is estimated that at least half the patients with nonvalvular AF who are eligible for warfarin therapy do not receive it [6,7]. A forthcoming oral direct thrombin inhibitor, ximalegatran, was anticipated as a replacement for warfarin, and study results were promising [8]. However, concerns with regard to hepatotoxicity with long term use have been raised [9].A medical need still remains for a safe and effective oral anticoagulant that is easier than warfarin for physicians and patients to use on a long-term basis. In response to this unmet need a novel oral drug delivery technology that enables poorly absorbed molecules to be absorbed through the gastrointestinal tract w