Regulation of hepatic drug metabolism: role of the nuclear receptors PXR and CAR.

Recent advances in the molecular biology of nuclear receptors have revealed that the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are able to act as sensors for lipophilic xenobiotics, including therapeutic drugs. These receptors in turn regulate enzymes and transporters involved in drug metabolism and disposition in an adaptive fashion. An unexpected finding was that the PXR was able to recognize bile acids; transgenic animals lacking this receptor are at increased risk of bile acid-induced liver injury. These findings provide new insights into hepatic drug metabolism as well as mechanisms regulating cholesterol and bile acid homeostasis.