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Monoclonal Digoxin-Specific Antibodies Induce Dose-and Affinity-Dependent Plasma Digoxin Redistribution in Rats

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Abstract

The effect of three monoclonal digoxin-specific antibodies on total and free digoxin plasma disposition was studied in rats in order to determine the role of affinity constant (Ka) and dose. Thirty minutes after digoxin infusion, administration of a stoichiometrical dose of the 1CIO, 6C9 and 9F5 IgG (Ka = 6 109, 3.1 108 and 2.5 107 M−1, respectively) resulted in a plasma digoxin increase linearly related to Ka. The mean free plasma digoxin was 0.6 ± 0.4, 7.8 ± 3.3 and 43 ± 22 % respectively after 1C10, 6C9, and 9F5 IgG infusion in comparison to 70 ± 9% in the control group. When the IgG:digoxin ratio increased from 1 to 5, plasma digoxin Cmax and AUCT also increased as a function of both affinity (Ka) and dose (N), but not linearly. The product of NKa defined an immunoreactivity factor that was well fitted to the digoxin redistribution parameters (Cmax and AUCT) by a Hill equation.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, U26, Hôpital Fernand Widal, Paris, France

    Nathalie J. Cano, Alain E. Sabouraud, Kamel Benmoussa & Jean-Michel G. Scherrmann

  2. Faculté de Pharmacie, Unité de Recherche en Immunologie, Montpellier, France

    Francoise Roquet, Isabelle Navarro-Teulon & Jean-Claude Mani

Authors
  1. Nathalie J. Cano
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  2. Alain E. Sabouraud
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  3. Kamel Benmoussa
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  4. Francoise Roquet
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  5. Isabelle Navarro-Teulon
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  6. Jean-Claude Mani
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  7. Jean-Michel G. Scherrmann
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Cano, N.J., Sabouraud, A.E., Benmoussa, K. et al. Monoclonal Digoxin-Specific Antibodies Induce Dose-and Affinity-Dependent Plasma Digoxin Redistribution in Rats. Pharm Res 12, 709–714 (1995). https://doi.org/10.1023/A:1016211626095

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  • DOI: https://doi.org/10.1023/A:1016211626095

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