title: Recombinant desulphatohirudin (CGP 39393) anticoagulant and antithrombotic properties in vivo.
abstract: The effects of the newly available biotechnology product, recombinant desulphatohirudin (CGP 39393) have been investigated in rats. This highly potent and selective thrombin inhibitor exhibited marked anticoagulant properties with controllable titration of anticoagulant effect, as measured by activated partial thromboplastin time (APTT), up to nearly four times control values. Furthermore, CGP 39393 exhibited impressive antithrombotic activity in vivo. In an arteriovenous shunt model of thrombus formation on a cotton-thread, the compound was capable of complete inhibition of thrombus development (ED50 = 0.3 mg/kg i.v. and 1.0 mg/kg s.c.). Venous stasis thrombosis was also highly susceptible to inhibition by CGP 39393 (ED50 = 0.01 mg/kg i.v. and 0.45 mg/kg s.c.). Comparison of the anticoagulant and antithrombotic activities of the compound shows that potent antithrombotic effects (83-97% inhibition in the rat shunt model) are achieved within the generally acceptable range of anticoagulation. These results suggest a clear potential for this new agent in the clinical treatment of thrombotic disease.
authors.affiliation: Thrombosis Research, CIBA-GEIGY Pharmaceuticals, West Sussex, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Talbot
authors.forename: J
authors.initials: J
authors.lastname: Ambler
authors.forename: K D
authors.initials: KD
authors.lastname: Butler
authors.forename: V S
authors.initials: VS
authors.lastname: Findlay
authors.forename: K A
authors.initials: KA
authors.lastname: Mitchell
authors.forename: R F
authors.initials: RF
authors.lastname: Peters
authors.forename: M F
authors.initials: MF
authors.lastname: Tweed
authors.forename: R B
authors.initials: RB
authors.lastname: Wallis
mesh_terms: D000818:Animals; D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D001166:Arteriovenous Shunt, Surgical; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D008026:Ligation; D008297:Male; D010314:Partial Thromboplastin Time; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D014682:Vena Cava, Inferior
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D006629:Hirudins; D011994:Recombinant Proteins; C060225:desirudin