Related Experiment Video
Updated: Mar 27, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Regulation of drug-metabolizing enzymes by local and systemic liver injuries
Yan Guo1,2, Bingfang Hu1,3, Yang Xie1
1a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.
Introduction:
Drug metabolism and disposition are critical in maintaining the chemical and functional homeostasis of xenobiotics/drugs and endobiotics. The liver plays an essential role in drug metabolism and disposition due to its abundant expression of drug-metabolizing enzymes (DMEs) and transporters. There is growing evidence to suggest that many hepatic and systemic diseases can affect drug metabolism and disposition by regulating the expression and/or activity of DMEs and transporters in the liver.
Areas Covered:
This review focuses on the recent progress on the regulation of DMEs by local and systemic liver injuries. Liver ischemia and reperfusion (I/R) and sepsis are used as examples of local and systemic injury, respectively. The reciprocal effect of the expression and activity of DMEs on animals' sensitivity to local and systemic liver injuries is also discussed.
Expert Opinion:
Local and systemic liver injuries have a major effect on the expression and activity of DMEs in the liver. Understanding the disease effect on DMEs is clinically important due to the concern of disease-drug interactions. Future studies are necessary to understand the mechanism by which liver injury regulates DMEs. Human studies are also urgently needed in order to determine whether the results in animals can be replicated in human patients.
Related Concept Videos
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Drug toxicity: Idiosyncratic Reactions
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Pharmacogenetics of Drug Metabolism: Overview

