Cytochrome P-450 3A4 (CYP3A4) contributes to the metabolism of approximately half the drugs in clinical use today. The aim of the present study was to determine the frequency of the CYP3A4*1B, *2, *4, *5, and *18 alleles amongst both Tepehuan Amerindians, a native group that has inhabited northern Mexico for thousands of years, and Mestizo Mexicans, and to compare the data with those of other p...

CYP3A4, an isoform of cytochrome P450 enzymes, is responsible for the metabolism of 45% to 60% of currently prescribed drugs. It has been shown that CYP3A4*1G, a single nucleotide polymorphism (SNP), affects the enzymatic activity of CYP3A4. Sufentanil, a synthetic opioid commonly used for the induction and maintenance of general anesthesia, analgesia, and sedation, is mainly metabolized by CYP...

An anti-peptide antibody targeted against residues 253 to 269 of human CYP3A4 was produced that specifically and potently inhibited its activity in human hepatic microsomal fraction (>90%). The function of this region in P450 catalysis was investigated. Antibody binding to CYP3A4 was unable to affect the magnitude of the Type I spectrum on addition of testosterone. It also had no effect on the ...

Drug-induced hepatotoxicity is an important cause for disapproval, limitations of use, or withdrawal of drugs, and there is a high need for reproducible in vitro systems that can predict such toxicity. In this study, we show that confluent growth of the human hepatoma cell line Huh7 up to 5 weeks results in increased gene expression of several cytochromes P450 (P450s), UDP-glucuronosyltransfera...

Previous reports have suggested that the nuclear receptors vitamin D receptor (VDR), peroxisome proliferator-activated receptor α (PPARα), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are involved in the regulation of the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 expression in adults. The aim of this study was to investigate the gene expression of CYP3A4 and the...

Cytochromes P450 (P450s) interact with redox transfer proteins, including P450 reductase (CPR) and cytochrome b(5) (b5), all being membrane-bound. In multiple in vitro systems, P450-P450 interactions also have been observed, resulting in alterations in enzymatic activity. The current work investigated the effects and mechanisms of interaction between CYP2C9 and CYP3A4 in a reconstituted system....

the environmental procarcinogen which are responcible for carcinogenesis, to form the proximate carcinogen, they require metabolic activation by drug metabolizing enzymes. the cyp3a subfamily enzymes play an important role in elimination of drugs. the substrates for cyp3a4 enzyme include drugs, and endogenous substances. therefore, allelic changes in the coding regions of cyp3a4, increases the ...

P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) are expressed in the intestine and are associated with drug absorption and metabolism. Pregnane X receptor (PXR) is the key molecule that regulates the expression of P-gp and CYP3A4. Given that PXR activity is regulated by a variety of compounds, it is possible that unknown PXR activators exist among known medicines. Kampo is a Japanese tra...

Conversion of the carbamazepine metabolite 3-hydroxycarbamazepine (3-OHCBZ) to the catechol 2,3-dihydroxycarbamazepine (2,3-diOHCBZ) followed by subsequent oxidation to a reactive o-quinone species has been proposed as a possible bioactivation pathway in the pathogenesis of carbamazepine-induced hypersensitivity. Initial in vitro phenotyping studies implicated CYP3A4 as a primary catalyst of 2,...

Our previous report showed that L754.394 and valspodar (PSC833) are potent inhibitors of midazolam hydroxylation in human jejunum microsomes and vectorial transport of vinblastine in Caco-2 cells, respectively. In the present study, to directly examine the interactions of these compounds as well as other substrates with CYP3A4 and P-glycoprotein (P-gp), we performed in vitro inhibition studies ...