title: A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?
abstract: Pregnane X receptor (PXR, NR112) is a xenobiotic receptor whose primary function is to regulate the expression of drug-metabolizing enzymes (DMEs) and drug transporters. Drug-induced PXR activation and subsequent enzyme and transporter induction has been proposed to be an important mechanism for the drug-drug interactions. In addition to activating PXR, many pharmaceutical chemicals can also function as reversible or irreversible inhibitors of DMEs, which may also impact the pharmacokinetics and pharmacodynamics (PK/PD) of drugs. Therefore, we cannot simply conclude that the PXR-induced alteration in enzyme expression always reflects functional changes. We should consider both PXR activation and DMEs inhibition to improve drug safety in the clinic.
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Yuan
authors: Y
authors: Wei
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Chenxiao
authors: C
authors: Tang
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Vinayak
authors: V
authors: Sant
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Song
authors: S
authors: Li
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Samuel M
authors: SM
authors: Poloyac
authors: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, 306 Salk Pavilion, 335 Sutherland Drive, Pittsburgh, PA 15261, USA.
authors: Wen
authors: W
authors: Xie
keywords: Drug metabolism; Enzyme inhibition; Gene regulation; Nuclear receptor