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Thromb Haemost 1997; 77(05): 1025-1033
DOI: 10.1055/s-0038-1656097
Animal models
Schattauer GmbH Stuttgart

Comparison of Dose Regimens for the Administration of Recombinant Pro-urokinase in a Canine Thrombosis Model

Authors

  • Sandra E Burke

    1   The Department of General Pharmacology, Abbott Laboratories, Abbott Park, Illinois, USA and

  • Nathan L Lubbers

    1   The Department of General Pharmacology, Abbott Laboratories, Abbott Park, Illinois, USA and

  • Richard A Nelson

    1   The Department of General Pharmacology, Abbott Laboratories, Abbott Park, Illinois, USA and

  • Jack Henkin

    2   The Department of Thrombolytic Venture, Abbott Laboratories, Abbott Park, Illinois, USA
Further Information

Publication History

Received 30 January 1996

Accepted after revision 11 December 1996

Publication Date:
11 July 2018 (online)

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Summary

Pro-urokinase represents an important addition to the array of thrombolytic drugs currently available for clinical use because of its high clot specificity but distinctly different mechanism compared with that of t-PA. Recombinant pro-urokinase (r-proUK) is a single-chain precursor of high molecular weight urokinase which has been expressed in a mouse myeloma cell line. The present study was conducted to determine the dosing regimen which would produce optimal clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radiolabelled clot which was formed in the heat-damaged femoral arteries of 39 male beagle dogs. The animals were divided into six heparinized treatment groups, each receiving one of five dosing regimens or the vehicle for r-proUK. The total dose (80,000 U/kg) was divided into an initial loading bolus, followed by either a second bolus or by infusions for various time periods, as shown below:

It was concluded that optimal clot lysis and restoration of femoral flow was accomplished using a regimen in which 50% of the dose was given as a bolus, followed immediately by the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose used in this study, r-proUK did not produce degradation of fibrinolytic or hemostatic plasma proteins.