Comparison of dose regimens for the administration of recombinant pro-urokinase in a canine thrombosis model

Sandra E. Burke*, Nathan L. Lubbers, Richard A. Nelson, Jack Henkin

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations

    Abstract

    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. 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.

    Original languageEnglish (US)
    Pages (from-to)1025-1030
    Number of pages6
    JournalThrombosis and Haemostasis
    Volume77
    Issue number5
    StatePublished - May 1 1997

    ASJC Scopus subject areas

    • Hematology

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