Use of in vitro transporter assays to understand hepatic and renal disposition of new drug candidates

Expert Opin Drug Metab Toxicol. 2005 Oct;1(3):409-27. doi: 10.1517/17425255.1.3.409.

Abstract

Hepatic and renal transporters contribute to the uptake, secretion and reabsorption of endogenous compounds, xenobiotics and their metabolites and have been implicated in drug-drug interactions and toxicities. Characterising the renal and hepatic disposition of drug candidates early in development would lead to more rational drug design, as chemotypes with 'ideal' pharmacokinetic characteristics could be identified and further refined. Because transporters are often organ specific, 'custom' transporter panels need to be identified for each major organ and chemotype to be evaluated, and appropriate studies planned. This review outlines the major renal and hepatic transporters and some of the in vitro transporter reagents, assays and processes that can be used to evaluate the renal and hepatic disposition of new chemical entities during drug discovery and development.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Humans
  • Kidney / metabolism*
  • Liver / metabolism*
  • Pharmaceutical Preparations / metabolism*
  • Xenobiotics / metabolism

Substances

  • Carrier Proteins
  • Pharmaceutical Preparations
  • Xenobiotics