DRUG-THERAPY - PHARMACOLOGICAL PROPERTIES OF HIRUDIN AND ITS DERIVATIVES - POTENTIAL CLINICAL ADVANTAGES OVER HEPARIN

Hirudin and its derivatives represent the first parenteral anticoagula nts introduced since the discovery of heparin in the early 1900s. Hiru din, the naturally occurring anticoagulant of the leech, is a single p eptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant fo rms of hirudin (r-hirudin) in sufficient quantities for therapeutic us e. Hirudin is a potent thrombin-specific inhibitor that forms equimola r complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many yea rs. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no dire ct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preven ting or treating venous thromboembolism is very preliminary. However, r-hirudin achieved promising results in patients with unstable angina, or following coronary angioplasty. In patients with acute myocardial infarction, 3 important clinical trials were stopped because of an exc ess of bleeding complications. At present, the discovery of a r-hirudi n regimen that is more efficacious than heparin and at least as safe n eeds a reappraisal of the drug in further trials.