title: Pharmacological properties of hirudin and its derivatives. Potential clinical advantages over heparin.
abstract: Hirudin and its derivatives represent the first parenteral anticoagulants introduced since the discovery of heparin in the early 1900s. Hirudin, the naturally occurring anticoagulant of the leech, is a single peptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant forms of hirudin (r-hirudin) in sufficient quantities for therapeutic use. Hirudin is a potent thrombin-specific inhibitor that forms equimolar complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many years. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no direct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preventing 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 excess of bleeding complications. At present, the discovery of a r-hirudin regimen that is more efficacious than heparin and at least as safe needs a reappraisal of the drug in further trials.
authors.affiliation: Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Monreal
authors.forename: J
authors.initials: J
authors.lastname: Costa
authors.forename: P
authors.initials: P
authors.lastname: Salva
mesh_terms: D000789:Angina, Unstable / Q000188:drug therapy*; D015906:Angioplasty, Balloon, Coronary; D000991:Antithrombins / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000188:drug therapy*
chemical_list: D000991:Antithrombins; D006629:Hirudins