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The effect of ipriflavone and its main metabolites on theophylline biotransformation

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Summary

The effect of ipriflavone and its major metabolites, 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on theophylline metabolism was examined in vitro in human liver microsomes. The compounds inhibited the N-demethylation to 1- or 3-methylxanthine, the major pathway of theophylline metabolism. The effect showed concentration dependence. The oxidation of theophylline to 1,3-dimethyluric acid was slightly affected by ipriflavone and its metabolites and the effect was non-specific. Results indicate that the reduction of theophylline clearance by concomitant ipriflavone administration observed by Takahashi et al. [Takahashi J., Kawakatsu K., Wakayama T., Sawaoka H. (1992): Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. Eur. J. Clin. Pharmacol., 43, 207–208] is primarily due to an interaction of the inhibitory ipriflavone and/or its metabolites with cytochrome P450 enzyme(s) that mediate N-demethylation of theophylline.

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Authors and Affiliations

  1. Central Research Institute for Chemistry, Hungarian Academy Sciences, PO Box 17, 1525, Budapest, Hungary

    K. Monostory & L. Vereczkey

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  1. K. Monostory
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  2. L. Vereczkey
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Monostory, K., Vereczkey, L. The effect of ipriflavone and its main metabolites on theophylline biotransformation. European Journal of Drug Metabolism and Pharmacokinetics 21, 61–66 (1996). https://doi.org/10.1007/BF03190279

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  • DOI: https://doi.org/10.1007/BF03190279

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