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Tirofiban versus abciximab: tirofiban is administered at suboptimal dosages when evaluated in an arterial thrombosis model in non-human primates

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Abstract

To prevent thrombosis in high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention for re-vascularisation, concomitant administration of a glycoprotein IIb/IIIa inhibitor, such as abciximab, tirofiban or eptifibatide, is recommended. Abciximab and eptifibatide are mostly preferred over tirofiban, which is less effective in preventing ischaemic events. We compared the efficacy and bleeding potential of escalating doses of tirofiban and abciximab in non-human primates. The efficacy of tirofiban and abciximab in inhibiting cyclic flow reductions (CFRs) was tested in a high shear arterial thrombosis model. Bleeding was evaluated with the template bleeding time and an incision bleeding model. Abciximab completely inhibited arterial thrombosis after injection of its therapeutic bolus dose. With tirofiban, a dose three times higher than the recommended therapeutic dose caused weak inhibition characterised by a return of CFRs after re-injury. At nine times the recommended therapeutic dose, complete inhibition was observed, and the efficacy of tirofiban was comparable to abciximab at its therapeutic bolus dose. Blood loss was less than with abciximab at its effective dose. In this model, tirofiban compared favourably with abciximab, although only at a dose of 3–9 times the therapeutic dose, and caused less bleeding than abciximab.

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Acknowledgments

Daleen Struwig, medical writer, Faculty of Health Sciences, University of the Free State, for assistance with technical and editorial preparation of the manuscript. The research was funded by departmental funds provided by the Department of Haematology and Cell Biology, Faculty of Health Sciences, University of the Free State.

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Preclinical Drug Testing Facility, Department of Haematology and Cell Biology (G2), Faculty of Health Sciences, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa

    Walter J. Janse van Rensburg & Jan P. Roodt

  2. Animal Research Facility, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa

    Seb Lamprecht

  3. National Health Laboratory Services Tertiary Laboratory, Universitas Academic Hospital, Bloemfontein, South Africa

    Jan P. Roodt & S. Muriel Meiring

  4. Department of Haematology and Cell Biology (G2), Faculty of Health Sciences, University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa

    S. Muriel Meiring & Philip N. Badenhorst

Authors
  1. Walter J. Janse van Rensburg
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  2. Jan P. Roodt
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  3. Seb Lamprecht
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  4. S. Muriel Meiring
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  5. Philip N. Badenhorst
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Correspondence to Walter J. Janse van Rensburg.

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van Rensburg, W.J.J., Roodt, J.P., Lamprecht, S. et al. Tirofiban versus abciximab: tirofiban is administered at suboptimal dosages when evaluated in an arterial thrombosis model in non-human primates. Clin Exp Med 12, 257–263 (2012). https://doi.org/10.1007/s10238-011-0171-4

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  • DOI: https://doi.org/10.1007/s10238-011-0171-4

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