Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions

Int J Mol Sci. 2018 Mar 14;19(3):855. doi: 10.3390/ijms19030855.

Abstract

Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics. Growing evidences suggest that the transport function of OATP1B1 and OATP1B3 can be regulated at various levels such as genetic variation, transcriptional and post-translational regulation. The present review summarizes the up to date information on the regulation of OATP1B1 and OATP1B3 transport function at different levels with a focus on potential impact on OATP-mediated DDIs.

Keywords: OATP1B1; OATP1B3; lysosome inhibitor; post-translation; proteasome inhibitor; protein degradation; transcription.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Interactions
  • Humans
  • Liver / metabolism
  • Membrane Transport Modulators / pharmacology*
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism*
  • Protein Processing, Post-Translational*

Substances

  • Membrane Transport Modulators
  • Organic Anion Transporters