Pharmacology and clinical potential of direct thrombin inhibitors.
Direct thrombin inhibitors represent a new class of anticoagulants that bind directly to thrombin and block the enzyme's interactions with its substrates. These agents have been developed, at least in part, to overcome the limitations of heparin and vitamin K antagonists. This paper (a) reviews why thrombin is an ideal target for new anticoagulants, (b) describes the pharmacological profiles of the various direct thrombin inhibitors, (c) outlines the potential mechanistic advantages of parenteral direct thrombin inhibitors over heparin, (d) defines the potential benefits of ximelagatran, the first orally active direct thrombin inhibitor, over vitamin K antagonists, and (e) provides clinical perspective on the strengths and weaknesses of the various parenteral and oral direct thrombin inhibitors.
Linkins
Lori-Ann
LA
McMaster University and Henderson Research Centre, Hamilton, Ontario, L8V 1C3, Canada.
Weitz
Jeffrey I
JI
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000097:blood / Q000188:drug therapy; D006801:Humans; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D013917:Thrombin