THE EFFECT OF IPRIFLAVONE AND ITS MAIN METABOLITES ON THEOPHYLLINE BIOTRANSFORMATION

The effect of ipriflavone and its major metabolites, 7-hydroxy-isoflav one 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 th eophylline metabolism. The effect showed concentration dependence. The oxidation of theophylline to 1,3-dimethyiuric acid was slightly affec ted by ipriflavone and its metabolites and the effect was non-specific . Results indicate that the reduction of theophylline clearance by con comitant ipriflavone administration observed by Takahashi et al. [Taka hashi J., Kawakatsu K., Wakayama T., Sawaoka H. (1992) : Elevation of serum theophylline levels by ipriflavone in a patient with chronic obs tructive pulmonary disease. fur. J. Clin. Pharmacol., 43, 207-208] is primarily due to an interaction of the inhibitory ipriflavone and/or i ts metabolites with cytochrome P450 enzyme(s) that mediate N-demethyla tion of theophylline.