Noninvasive preclinical and clinical imaging of liver transporter function relevant to drug-induced liver injury

Research output: ResearchChapter

  • External authors:
  • J. Gerry Kenna
  • John C. Waterton
  • Andreas Baudy
  • Catherine D.G. Hines
  • Paul Hockings
  • Manishkumar Patel
  • Steven Sourbron
  • Sabina Ziemian
  • Gunnar Schuetz

Abstract

Imaging technologies can evaluate many different biological processes in vitro (in cell culture models) and in vivo (in animals and humans), and many are used routinely in investigation of human liver diseases. Some of these methods can help understand liver toxicity caused by drugs in vivo in animals, and drug-induced liver injury (DILI) which arises in susceptible humans. Imaging could aid assessment of the relevance to humans in vivo of toxicity caused by drugs in animals (animal/human translation), plus toxicities observed using in vitro model systems (in vitro/in vivo translation). Technologies and probe substrates for quantitative evaluation of hepatobiliary transporter activities are of particular importance. This is due to the key role played by sinusoidal transporter mediated hepatic uptake in DILI caused by many drugs, plus the strong evidence that inhibition of the hepatic bile salt export pump (BSEP) can initiate DILI. Imaging methods for investigation of these processes are reviewed in this chapter, together with their scientific rationale, and methods of quantitative data analysis. In addition to providing biomarkers for investigation of DILI, such approaches could aid the evaluation of clinically relevant drug–drug interactions mediated via hepatobiliary transporter perturbation.

Bibliographical metadata

Original languageEnglish
Title of host publicationDrug-Induced Liver Toxicity
Place of PublicationNew York, NY
PublisherHumana Press, Inc.
Pages627-651
Number of pages25
ISBN (Electronic)9781493976775
ISBN (Print)9781493976768
DOIs
StatePublished - 21 Mar 2018

Publication series

NameMethods in Pharmacology and Toxicology
Number9781493976768
ISSN (Print)1557-2153
ISSN (Electronic)1940-6053