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Thein vitro metabolism of mebendazole by pig, rat and dog liver fractions

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Summary

Mebendazole-14C was incubated with the 10,000g and 100,000g supernatant fractions and the microsomal fractions of pig, rat and dog liver. The metabolism progressed remarkably slowly. The metabolites were separated by extraction and thin-layer chromatography, and characterized by comparative thin-layer chromatography and mass spectrometry. The major metabolite was methyl[5-(α-hydroxy-α-phenylmethyl)-lH-benzimidazol-2-yl]carbamate, resulting from a reduction of the ketone of mebendazole. After 4 hours, this metabolite accounted for 50, 58 and 93 % of the total radioactivity for the pig, rat and dog 10,000g supernatant fractions respectively. The 100,000g supernatant fractions as well as the microsomal fractions of the three different species contained reductases able to reduce the ketone of mebendazole. A second metabolite (2-amino-lHyl)phenylmethanone, resulting from a carbamate hydrolysis, was only formed with the 10,000 g supernatant and the microsomal fraction of pig liver (about 5 % after 4 hours); this metabolic pathway was shown to be inhibited by SKF-525 A.

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Authors and Affiliations

  1. Research Laboratoria, Dept. of Drug Metabolism Janssen Pharmaceutica n.v., Turnhoutsebaan 30, B-2340, Beerse, Belgium

    W. E. G. Meuldermans, R. M. A. Hurkmans, W. F. J. Lauwers & J. J. P. Heykants

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  1. W. E. G. Meuldermans
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  2. R. M. A. Hurkmans
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  3. W. F. J. Lauwers
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  4. J. J. P. Heykants
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Meuldermans, W.E.G., Hurkmans, R.M.A., Lauwers, W.F.J. et al. Thein vitro metabolism of mebendazole by pig, rat and dog liver fractions. European Journal of Drug Metabolism and Pharmacokinetics 1, 35–40 (1976). https://doi.org/10.1007/BF03192277

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