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Cleavage of digoxigenin digitoxosides by rat liver microsomes

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An Erratum to this article was published on 01 January 1981

Summary

Microsomal monoxygenases can oxidize the axial hydroxyl of the terminal digitoxosyl of digoxin (dg-3), digoxigenin bis-, and digoxigenin mono-digitoxoside (dg-2 and dg-1, respectively) to an oxo-group. The corresponding metabolites (15′-dehydro-dg-3, 9′-dehydro-dg-2, and 3′-dehydro-dg-l, respectively) have been identified by chromatographic and chemical methods. Only after this oxibation the terminal sugar can be split off, presumably by β-elimination. Therefore, for the degradation of dg-3 three successive cytochrome P450 catalyzed oxidations are necessary before digoxigenin (dg-0) can be obtained. The highest oxibation rate was observed with dg-1 (120–150 pmoles/mg microsomal protein/min) and by far the lowest with dg-2 (6–7 pmoles/min) as the substrate (concentration was 30/μM). The latter may contribute to the effect that dg-2 is the main dg-3 metabolite in vivo. Pretreatment of rats with canrenoate enhanced the microsomal oxidation of dg-3, dg-2, and dg-1 by a factor of 3.2, 2.3 and 1.3, respectively. In contrast, there was no increase after pretreatment with phénobarbital.

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Authors and Affiliations

  1. Department of Pharmacology, University of Hamburg, Martinistrasse 52, 2000, Hamburg 20, W. Germany

    A. Schmoldt & B. Ahsendorf

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  1. A. Schmoldt
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  2. B. Ahsendorf
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An erratum to this article is available at http://dx.doi.org/10.1007/BF03189509.

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Schmoldt, A., Ahsendorf, B. Cleavage of digoxigenin digitoxosides by rat liver microsomes. European Journal of Drug Metabolism and Pharmacokinetics 5, 225–232 (1980). https://doi.org/10.1007/BF03189468

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  • DOI: https://doi.org/10.1007/BF03189468

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