Assessment of reactive metabolites in drug-induced liver injury

Arch Pharm Res. 2011 Nov;34(11):1879-86. doi: 10.1007/s12272-011-1108-x. Epub 2011 Dec 3.

Abstract

The aim of the current review is to summarize present methods used for the determination of reactive metabolites, which can predict drug-induced liver injury (DILI) in drug discovery and development. DILI is one of the most frequent reasons for the withdrawal of an approved drug from the market, and it accounts for up to 50% of acute liver failure cases. This review is structured into three sections. The first section is a general overview of the relationship between drug metabolism and liver injury. The second section introduces in vitro methods for the assessment of reactive metabolites for drug discovery and development. In the third section, limitations and future directions for the development of methods for predicting DILI are described.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biotransformation
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Evaluation, Preclinical / methods
  • Drugs, Investigational / adverse effects*
  • Drugs, Investigational / chemistry
  • Drugs, Investigational / pharmacokinetics*
  • Drugs, Investigational / pharmacology
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Glucuronides / metabolism
  • Glutathione / chemistry
  • Humans
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism*

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Drugs, Investigational
  • Enzyme Inhibitors
  • Glucuronides
  • Cytochrome P-450 Enzyme System
  • Glutathione