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.
Key words
Recombinant desulphatohirudin - CGP 39393 - Hirudin - Man - Thrombin inhibitor - Anticoagulant
- Antithrombotic
