Ipriflavone as an inhibitor of human cytochrome P450 enzymes

K. Monostory, L. Vereczkey, Ferenc Lévai, István Szatmári

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

1 Reduction of theophylline metabolism and elimination were observed in a theophylline-treated patient during ipriflavone administration. After withdrawal of ipriflavone, the serum theophylline level decreased to an extent similar to that found before administration of ipriflavone. The effects of ipriflavone and its major metabolites 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on cytochrome P450 activities were studied in vitro in human liver microsomes from three donors. 2 Ipriflavone and 7-hydroxy-isoflavone competitively inhibited phenacetin O-deethylase and tolbutamide hydroxylase activity. The parent compound and its dealkylated metabolite were strong inhibitors exhibiting Ki values around 10-20 μM, while 7-(l-carboxy-ethoxy)-isoflavone had no effect on the cytochrome P450 activities investigated. 7-Hydroxy-isoflavone is the only one that influenced nifedipine oxidase activity. It competitively inhibited this activity with a K, value of 129.5 μM. 3 The steady state concentrations of ipriflavone and 7-hydroxy-isoflavone in plasma of patients receiving 3 × 200 mg daily doses of ipriflavone for 48 weeks were found to be 0.33 ± 0.32 μM and 1.44 ± 0.77 μM, respectively. 4 The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipriflavone may be due to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy-isoflavone with CYPIA2. On the other hand, our in vitro findings predict some more interaction with CYP2C9.

Original languageEnglish
Pages (from-to)605-610
Number of pages6
JournalBritish Journal of Pharmacology
Volume123
Issue number4
Publication statusPublished - 1998

Fingerprint

Isoflavones
Cytochrome P-450 Enzyme System
Theophylline
Phenacetin
ipriflavone
Tolbutamide
Liver Microsomes
Nifedipine
Mixed Function Oxygenases
Oxidoreductases
Tissue Donors
Serum

Keywords

  • Human cytochrome P450 enzymes
  • Inhibition
  • Ipriflavone

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ipriflavone as an inhibitor of human cytochrome P450 enzymes. / Monostory, K.; Vereczkey, L.; Lévai, Ferenc; Szatmári, István.

In: British Journal of Pharmacology, Vol. 123, No. 4, 1998, p. 605-610.

Research output: Contribution to journalArticle

Monostory, K. ; Vereczkey, L. ; Lévai, Ferenc ; Szatmári, István. / Ipriflavone as an inhibitor of human cytochrome P450 enzymes. In: British Journal of Pharmacology. 1998 ; Vol. 123, No. 4. pp. 605-610.
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