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Related Experiment Videos

Direct thrombin inhibitors for anticoagulation.

Edith A Nutescu1, Ann K Wittkowsky

  • 1Antithrombosis Service, College of Pharmacy, The University of Illinois at Chicago, Chicago, IL 60612, USA. enutescu@uic.edu

The Annals of Pharmacotherapy
|January 27, 2004
PubMed
Summary
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Direct thrombin inhibitors (DTIs) represent significant progress in anticoagulation therapy. The development of oral DTIs promises simpler and more effective prevention and treatment of thromboembolic disorders.

Area of Science:

  • Pharmacology
  • Hematology
  • Drug Development

Background:

  • Thrombin is a key target for anticoagulation due to its role in hemostasis.
  • Existing anticoagulants (warfarin, heparins) have limitations, driving the search for improved therapies.
  • Direct thrombin inhibitors (DTIs) offer a more specific approach to anticoagulation.

Purpose of the Study:

  • To review the progress in the development of direct thrombin inhibitors (DTIs).
  • To contextualize DTI development within existing anticoagulation strategies.
  • To identify challenges and advancements in DTI research.

Main Methods:

  • Comprehensive literature search of MEDLINE (1993-2003).
  • Inclusion of English-language articles, human, and relevant animal studies.

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  • Citation analysis of retrieved articles for additional relevant studies.

    • Main Results:

    • DTIs target thrombin, a critical factor in blood clot formation.
    • Current DTIs include lepirudin, bivalirudin, and argatroban, with ongoing research into oral agents like ximelagatran.
    • Key development challenges include achieving optimal binding affinity, thrombin specificity, inhibition of both free and clot-bound thrombin, and oral bioavailability.

    Conclusions:

    • Substantial progress has been achieved in the development of direct thrombin inhibitors.
    • The advent of orally administered DTIs holds potential for simplifying anticoagulation therapy for thrombosis prevention and treatment.