CYP3A4: 2 of 13 references for rifampin and 1 of 3 references for phenobarbital used midazolam. Note this is not a exhaustive list of all CYP inhibitors and only the genes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5 are considered. Interactions between polyphenols and CYP3A4 are important due to their potential implications for drug metabolism. Avoid concurrent use of strong CYP3A4 inhibitors. Potential interactions of polyphenols with CYP3A4. A. Gallic acid (3,4,5-trihydroxybenzoic acid), also a member of the polyphenols and is abundant in many beverages, for example, wine, tea, pomegranate juice and olive oil, has an inhibitory effect on androstenedione 6-β-hydroxylase activity in vitro (apparent value 70 μM), which is regarded as a marker for CYP3A enzyme activity [187]. enzymes that eliminate most of the drugs and toxins from our body An additional QSAR study based on five statistical tools identified a strong correlation between the n-octanol/water partition coefficient () and the binding affinity of compounds for CYP3A4 [124]. We are committed to sharing findings related to COVID-19 as quickly as possible. demonstrated inhibitory effects of polyphenols on human CYP3A4 and CYP2C9 activity in vitro [73]. Pan et al., “Herb-drug interactions and mechanistic and clinical considerations,”, F. Qiu, J. Jiang, Y. Ma et al., “Opposite effects of single-dose and multidose administration of the ethanol extract of danshen on CYP3A in healthy volunteers,”, R. Rahimi and M. Abdollahi, “An update on the ability of St. John's wort to affect the metabolism of other drugs,”, H. G. Xie and R. B. Kim, “St. We recently reached a similar conclusion using software to study docking of polyphenols, in which we observed a correlation between the values of ligands and their docking energies with CYP3A4 (CDOCKER energy expressed in Kcal/mole; Basheer and Kerem, unpublished data). This is consistent with findings that have demonstrated the importance of ligand hydrophobicity for interactions with these enzymes [38, 123, 124]. Some drugs, such as clarithromy-cin, itraconazole, and ketoconazole, are particularly potent inhibitors of CYP3A4; patients on these drugs may have mark- edly reduced CYP3A4 activity. • Cimetidine. However, to the best of our knowledge the research in this area is limited and additional data are needed. This information is generalized and not intended as specific medical advice. A. Williams, “, K. S. Lown, D. G. Bailey, R. J. Fontana et al., “Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression,”, J. C. Kolars, K. S. Lown, P. Schmiedlin-Ren et al., “CYP3A gene expression in human gut epithelium,”, C. S. Ferguson and R. F. Tyndale, “Cytochrome P450 enzymes in the brain: emerging evidence of biological significance,”, C. Ghosh, N. Marchi, N. K. Desai et al., “Cellular localization and functional significance of CYP3A4 in the human epileptic brain,”, F. P. Guengerich, “Cytochrome P-450 3A4: regulation and role in drug metabolism,”, Z. Huang, M. J. Fasco, H. L. Figge, K. Keyomarsi, and L. S. Kaminsky, “Expression of cytochromes P450 in human breast tissue and tumors,”, J. H. Lin, M. Chiba, and T. A. Baillie, “Is the role of the small intestine in first-pass metabolism overemphasized?”, M. F. Paine, H. L. Hart, S. S. Ludington, R. L. Haining, A. E. Rettie, and D. C. Zeldin, “The human intestinal cytochrome P450 ‘pie’,”, A. Galetin, M. Gertz, and J. The term nutraceutical is commonly used in Their study was based on 2,400 marketed drugs and made use of pair-wise comparisons of IC50 activity values for different substrates of CYP3A4. In another study, Stupans and coworkers provided additional evidence for the inhibition of CYP3A activity by gallic acid. Thus, consuming large amounts of resveratrol could theoretically increase the bioavailability of and risk of toxicity from drugs that undergo extensive first-pass metabolism by CYP3A4 [179]. These interactions can modulate the activity or expression of the enzyme. of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the Bergamottin is a component of grapefruit juice and a known CYP3A4 inhibitor at the enzymatic level; however, its effects on the CYP1A2, 2D6, and CYP3A4 at the transcriptional level are currently unknown. The involvement of microbiota in the metabolism of these compounds generally starts with the hydrolysis of polymeric, glycosylated and/or esterified polyphenols by brush border and/or microbial enzymes, which is a prerequisite for the absorption and bioactivity of most compounds [134–136]. Three Americans use dietary supplements daily and among cancer patients the rate is much higher [ 54.. Genistein and daidzein are found in soybean and hence are very abundant in many processed food products du plus nombre... 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