The effect of ipriflavone and its main metabolites on theophylline biotransformation

Monostory, Katalin; Vereczkey, L.

doi:10.1007/bf03190279

Cited by 3 publications

(1 citation statement)

References 7 publications

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“…Our previous work (Monostory & Vereczkey, 1996) showed an inhibitory effect of ipriflavone and its major metabolites, 7‐hydroxy‐isoflavone and 7‐(1‐carboxy‐ethoxy)‐isoflavone, on theophylline metabolism in human liver microsomes. The compounds primarily decreased the N‐demethylation to 1‐ or 3‐methyl‐xanthine, the major pathways of theophylline metabolism.…”

Section: Introductionmentioning

confidence: 98%

Ipriflavone as an inhibitor of human cytochrome P450 enzymes

Monostory

Vereczkey

Lévai

et al. 1998

British J Pharmacology

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1 Reduction of theophylline metabolism and elimination were observed in a theophylline-treated patient during ipri¯avone administration. After withdrawal of ipri¯avone, the serum theophylline level decreased to an extent similar to that found before administration of ipri¯avone. The e ects of ipri¯avone and its major metabolites 7-hydroxy-iso¯avone and 7-(1-carboxy-ethoxy)-iso¯avone on cytochrome P450 activities were studied in vitro in human liver microsomes from three donors. 2 Ipri¯avone and 7-hydroxy-iso¯avone competitively inhibited phenacetin O-deethylase and tolbutamide hydroxylase activity. The parent compound and its dealkylated metabolite were strong inhibitors exhibiting K i values around 10 ± 20 mM, while 7-(1-carboxy-ethoxy)-iso¯avone had no e ect on the cytochrome P450 activities investigated. 7-Hydroxy-iso¯avone is the only one that in¯uenced nifedipine oxidase activity. It competitively inhibited this activity with a K i value of 129.5 mM. 3 The steady state concentrations of ipri¯avone and 7-hydroxy-iso¯avone in plasma of patients receiving 36200 mg daily doses of ipri¯avone for 48 weeks were found to be 0.33+0.32 mM and 1.44+0.77 mM, respectively. 4 The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipri¯avone may be due to a competitive interaction of ipri¯avone or its metabolite, 7-hydroxy-iso¯avone with CYP1A2. On the other hand, our in vitro ®ndings predict some more interaction with CYP2C9.

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Section: Introductionmentioning

confidence: 98%

Ipriflavone as an inhibitor of human cytochrome P450 enzymes

Monostory

Vereczkey

Lévai

et al. 1998

British J Pharmacology

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Antimutagenic activity of ipriflavone against the DNA-damage induced by cyclophosphamide in mice

Delarmelina

Dutra

Batitucci

2014

Food and Chemical Toxicology

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In the present study we evaluated the potential of ipriflavone against the cytotoxic and mutagenic effects induced by cyclophosphamide chemotherapeutic agent in bone marrow cells of mice, using the micronucleus assay in vivo on cells of bone marrow. The study was performed following three protocols: pre-treatment, simultaneous treatment and post treatment. The results demonstrated that ipriflavone has a protective effect against mutagenicity induced by cyclophosphamide in the pre-treatment and post-treatment and against the cytotoxicity in all treatments. There was variation between the genders in some of the experimental groups. To evaluate their possible mechanisms of action, it was performed the DPPH assay, which showed no ability to donate hydrogens, suggesting that it acts through other mechanisms. Due to its ability to prevent chromosomal damage, ipriflavone is likely to open an interest field concerning its possible the use in clinical applications.

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Characterization of cytochrome P450s mediating ipriflavone metabolism in human liver microsomes

Moon

Kim

et al. 2007

Xenobiotica

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Ipriflavone, a synthetic flavonoid for the prevention and treatment of osteoporosis, has been reported to be extensively metabolized in man to seven metabolites (M1-M7). This study was performed to characterize the human liver cytochrome P450s (CYP) responsible for the metabolism of ipriflavone. Hydroxylation at the beta-ring to M3, O-dealkylation to M1 and oxidation at isopropyl group to M4 and M5 are major pathways for ipriflavone metabolism in three different human liver microsome preparations. The specific CYPs responsible for ipriflavone oxidation to the active metabolites, M1, M3, M4 and M5 were identified using a combination of correlation analysis, immuno-inhibition, chemical inhibition in human liver microsomes and metabolism by expressed recombinant CYP enzymes. The inhibitory potencies of ipriflavone and its five metabolites, M1-M5 on seven clinically important CYPs were investigated in human liver microsomes. Our results demonstrate that CYP3A4 plays the major role in O-dealkylation of ipriflavone to M1 and CYP1A2 plays a dominant role in the formation of M3, M4 and M5. Ipriflavone and/or its five metabolites were found to inhibit potently the metabolism of CYPs 1A2, 2C8, 2C9 and 2C19 substrates.

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The effect of ipriflavone and its main metabolites on theophylline biotransformation

Cited by 3 publications

References 7 publications

Ipriflavone as an inhibitor of human cytochrome P450 enzymes

Ipriflavone as an inhibitor of human cytochrome P450 enzymes

Antimutagenic activity of ipriflavone against the DNA-damage induced by cyclophosphamide in mice

Characterization of cytochrome P450s mediating ipriflavone metabolism in human liver microsomes

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