The effect of ipriflavone and its main metabolites on theophylline biotransformation.
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.
Monostory
K
K
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.
Vereczkey
L
L
D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D016723:Bone Remodeling; D001993:Bronchodilator Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007529:Isoflavones / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D013806:Theophylline / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D000700:Analgesics; D001993:Bronchodilator Agents; D007529:Isoflavones; C018986:ipriflavone; D013806:Theophylline