The role of hepatic transporters in drug elimination

Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):363-79. doi: 10.1517/17425255.4.4.363.

Abstract

Background: Hepatic drug transporters of the solute carrier (OATPs, OAT2, OCT1, NTCP) and ABC transporter superfamilies (MDR1, MRPs, BCRP, BSEP) can significantly modulate drug ADME routes.

Objective: The currently available literature was reviewed with focus on hepatic drug transporters, related drug-drug interactions and available tools for transporter assessment and extrapolation to in vivo.

Conclusions: Hepatic drug transporters have gained additional importance in drug clearance by optimization for basic DMPK properties early on in drug research. However, the lack of selective substrates and inhibitors, proper assessment of the kinetic properties due to interfering passive permeability and multiple binding sites, as well as endogenous transporters present in many cellular assays, are some of the hurdles in studying active drug transport processes. Therefore, data from these in vitro assays have to be carefully evaluated to allow sound extrapolation to the in vivo situation.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions / metabolism
  • Humans
  • Liver / metabolism*
  • Membrane Transport Proteins / physiology*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics

Substances

  • Membrane Transport Proteins
  • Pharmaceutical Preparations