Orphan nuclear receptor-mediated xenobiotic regulation in drug metabolism

The regulation of drug-metabolizing enzymes and transporters has an important role in drug metabolism and many human diseases. The genes that encode these enzymes and transporters are inducible by numerous xenobiotics and endobiotics and the inducibility shows clear species specificity. In the past 4-5 years, orphan nuclear receptors such as PXR and CAR have been established as species-specific xeno-sensors that regulate the expression of many detoxifying enzymes and transporters. Their identification represents a major step forward in understanding the pharmacological and genetic control of the expression of drug-metabolizing enzymes and the implication of this regulation in drug metabolism, drug-drug interactions, and human diseases.