INTERACTION OF THEOPHYLLINE AND IPRIFLAVONE AT THE CYTOCHROME-P450 LEVEL

The effect of ipriflavone administered at a dose of 25 mg/kg and 100 m g/kg and coadministered with theophylline was investigated in selectiv e assays of particular P450 isoenzyme activities. Significant changes could be detected in the activities of CYP2E1 and CYP3A in liver micro somes from male Wistar rats treated with ipriflavone. Induction of CYP 2E1 was shown by aniline or p-nitrophenol hydroxylation as a result of ipriflavone treatment. Aniline hydroxylation activity of CYP2E1 was i nduced by theophylline + ipriflavone (100 mg/kg) coadministration as w ell. It should be noted that theophylline does not cause alteration in CYP2E1 activity. On the other hand, ipriflavone inhibited ethylmorphi ne and aminopyrine N-demethylation activities catalysed by CYP3A. An a dditional effect in the inhibition of aminopyrine N-demethylation coul d be observed in microsomes from theophylline + ipriflavone treated gr oups. Our results suggest that the decrease in theophylline metabolism and increasing lever of serum theophylline of theophylline-treated pa tient during ipriflavone administration [Takahashi J. et al. (1992): f ur. J. Clin. Pharmacol., 43, 207-208] may be related to CYP3A inhibiti on by ipriflavone.