There have been conflicting reports regarding the catalytic role of cytochrome P450 (CYP)3A5, which range from deeming it irrelevant to suggesting it is equally as important as CYP3A4, the most potent and abundant catalytic cytochrome enzyme in the human liver. This was partially attributed to the fact that CYP3A5 is highly polymorphic. However the importance of other underlying mechanisms rema...

CYP3A4, considered the most important enzyme in drug metabolism, is often involved in drug-drug interactions. When developing new drugs, appropriate markers for detecting CYP3A4 induction are needed. Our study compared endogenously formed 4b-hydroxycholesterol with the midazolam clearance in plasma and the 6b-hydroxycortisol/cortisol ratio in urine as markers for CYP3A4 induction. To this end, ...

The human cytochrome P4503A forms show expression patterns subject to developmental influence. CYP3A7 and CYP3A4 are generally classified as the major fetal and adult liver forms, respectively. However, characterization of CYP3A4, -3A5, and -3A7 developmental expression has historically been confounded by the lack of CYP3A isoform-specific antibodies or marker enzyme activities. Therefore, the ...

We have identified CYP2C19 and CYP3A4 as the principal cytochrome P450s involved in the metabolism of flunitrazepam to its major metabolites desmethylflunitrazepam and 3-hydroxyflunitrazepam. Human CYP2C19 and CYP3A4 mediated the formation of desmethylflunitrazepam with Km values of 11.1 and 108 microM, respectively, and 3-hydroxyflunitrazepam with Km values of 642 and 34.0 microM, respectively...

Between 45 and 60% of all drugs currently used are metabolized by the CYP3A4 protein. CYP3A4 expression in liver varies up to 60-fold in the general population, which can lead to ineffective drug therapy (high CYP3A4) or, on the other hand, to harmful drug reactions (low CYP3A4). Most of this variability has been attributed to genetic factors, but to date their identity remains unknown. Recentl...

BACKGROUND Gomisin G, isolated from herb Schisandra chinensis, exhibits anti-tumor activities. Therefore, Gomisin G is a drug candidate for anti-liver cancer therapy. AIMS To predict the metabolic behavior and metabolism-based drug-drug interaction of gomisin G. METHODS Molecular docking method was used. The crystal structure of CYP3A4 with the ligand ketoconazole was chosen from protein da...

CYP3A4, considered the most important enzyme in drug metabolism, is often involved in drug-drug interactions. When developing new drugs, appropriate markers for detecting CYP3A4 induction are needed. Our study compared endogenously formed 4β-hydroxycholesterol with the midazolam clearance in plasma and the 6β-hydroxycortisol/cortisol ratio in urine as markers for CYP3A4 induction. To this end, ...

We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6β-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was a...

More than 60 human immunodeficiency virus protease inhibitors were examined for the structure-activity relationship between metabolic stability, CYP3A4 inhibitory potency, and substrate-induced binding spectra with a ferric form of P450 in human liver microsomes. A positive relationship was found between CYP3A4 inhibitory potency and metabolic stability; namely, compounds that were more potent ...

The cytochrome P-450 3A (CYP3A) enzyme family is responsible for most of the drug metabolism in the human liver. In this study, we demonstrated the inductive effects of phenobarbital, rifampicin, carbamazepine, phenytoin, prednisolone, ciclosporin and clotrimazole on CYP3A4, CYP3A5 and CYP3A7 mRNA expression, and established the relationship between the expression of human glucocorticoid recept...