Thromb Haemost 1989; 61(01): 077-080
DOI: 10.1055/s-0038-1646530
Original Article
Schattauer GmbH Stuttgart

Recombinant Desulphatohirudin (CGP 39393) Anticoagulant and Antithrombotic Properties In Vivo

M D Talbot
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
J Ambler
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
K D Butler
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
V S Findlay
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
K A Mitchell
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
R F Peters
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
M F Tweed
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
,
R B Wallis
Thrombosis Research, Research Centre, CIBA- GEIGY Pharmaceuticals, Horsham, West Sussex, UK
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 08. Juli 1988

Accepted after revision 20. September 1988

Publikationsdatum:
24. Juli 2018 (online)

Summary

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.

 
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