Regulation of Hepatic Drug Metabolism: Role of the Nuclear Receptors PXR and CAR

Christopher Liddle; Bryan Goodwin

doi:10.1055/s-2002-30098

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2002; 22(2): 115-122
DOI: 10.1055/s-2002-30098

Regulation of Hepatic Drug Metabolism: Role of the Nuclear Receptors PXR and CAR

Christopher Liddle¹ , Bryan Goodwin²

¹Department of Clinical Pharmacology and Storr Liver Unit, Westmead Millennium Institute, University of Sydney, Westmead Hospital, Westmead, Australia
²Nuclear Receptor Systems Research, GlaxoSmithKline Inc., Research Triangle Park, North Carolina

Abstract

ABSTRACT

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.

KEYWORDS

Cytochrome P450 - bile acids - drug disposition - drug metabolism - nuclear receptor - pregnane X receptor - constitutive androstane receptor

Full Text

References

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