Biomaterial Database

Intestinal first-pass metabolism of CYP3A4 substrates. 2008

Motohiro Kato

Pre-clinical Research Department, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan. katomth@chugai-pharm.co.jp

Cytochrome P450 3A4 (CYP3A4) is present not only in the liver but also in the small intestine, where it functions as a barrier against xenobiotics. Some CYP3A4 substrates exhibit low bioavailability due to intestinal first pass metabolism. The AUCs of such CYP3A4 substrates are remarkably changed by the inhibition, induction, and saturation of CYP3A4 and so prediction of intestinal first-pass metabolism is important. In this article, factors affecting intestinal first-pass metabolism of drugs are reviewed, focusing on the intestinal metabolism by CYP3A. The methods to predict intestinal first-pass metabolism are also reviewed.

UI	MeSH Term	Description	Entries
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001628	Beverages	Liquids that are suitable for drinking. (From Merriam Webster Collegiate Dictionary, 10th ed)	Beverage
D051544	Cytochrome P-450 CYP3A	A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.	CYP3A,CYP3A4,CYP3A5,Cytochrome P-450 CYP3A4,Cytochrome P-450 CYP3A5,Cytochrome P-450IIIA,Cytochrome P450 3A,Cytochrome P450 3A4,Cytochrome P450 3A5,Erythromycin N-Demethylase,Taurochenodeoxycholate 6-alpha-Monooxygenase,3A5, Cytochrome P450,6-alpha-Monooxygenase, Taurochenodeoxycholate,Cytochrome P 450 CYP3A,Cytochrome P 450 CYP3A4,Cytochrome P 450 CYP3A5,Cytochrome P 450IIIA,Erythromycin N Demethylase,N-Demethylase, Erythromycin,P-450 CYP3A, Cytochrome,P-450 CYP3A4, Cytochrome,P-450 CYP3A5, Cytochrome,P-450IIIA, Cytochrome,P450 3A, Cytochrome,P450 3A5, Cytochrome,Taurochenodeoxycholate 6 alpha Monooxygenase
D019540	Area Under Curve	A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)	AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area
D032083	Citrus paradisi	A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.	Grapefruit,Toronja,Citrus x paradisi,Grapefruits,Toronjas
D065692	Cytochrome P-450 CYP3A Inhibitors	Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A.	CYP3A Inhibitor,CYP3A5 Inhibitor,CYP3A7 Inhibitor,Cyp3A4 Inhibitor,Cytochrome P-450 CYP3A Inhibitor,Cytochrome P-450 CYP3A4 Inhibitor,Cytochrome P-450 CYP3A5 Inhibitor,Cytochrome P-450 CYP3A7 Inhibitor,P450 CYP3A Inhibitor,P450 CYP3A4 Inhibitor,P450 CYP3A5 Inhibitor,P450 CYP3A7 Inhibitor,CYP3A Inhibitors,CYP3A4 Inhibitors,CYP3A5 Inhibitors,CYP3A7 Inhibitors,Cytochrome P-450 CYP3A4 Inhibitors,Cytochrome P-450 CYP3A5 Inhibitors,Cytochrome P-450 CYP3A7 Inhibitors,P450 CYP3A Inhibitors,P450 CYP3A4 Inhibitors,P450 CYP3A5 Inhibitors,P450 CYP3A7 Inhibitors,CYP3A Inhibitor, P450,CYP3A4 Inhibitor, P450,CYP3A5 Inhibitor, P450,CYP3A5 Inhibitors, P450,CYP3A7 Inhibitor, P450,CYP3A7 Inhibitors, P450,Cytochrome P 450 CYP3A Inhibitor,Cytochrome P 450 CYP3A Inhibitors,Cytochrome P 450 CYP3A4 Inhibitor,Cytochrome P 450 CYP3A4 Inhibitors,Cytochrome P 450 CYP3A5 Inhibitor,Cytochrome P 450 CYP3A5 Inhibitors,Cytochrome P 450 CYP3A7 Inhibitor,Cytochrome P 450 CYP3A7 Inhibitors,Inhibitor, CYP3A,Inhibitor, CYP3A5,Inhibitor, CYP3A7,Inhibitor, Cyp3A4,Inhibitor, P450 CYP3A,Inhibitor, P450 CYP3A4,Inhibitor, P450 CYP3A5,Inhibitor, P450 CYP3A7,Inhibitors, CYP3A,Inhibitors, CYP3A4,Inhibitors, CYP3A5,Inhibitors, CYP3A7,Inhibitors, P450 CYP3A,Inhibitors, P450 CYP3A4,Inhibitors, P450 CYP3A7