In Vivo Characterization of Interactions on Transporters

  • Hiroyuki Kusuhara
  • Kenta Yoshida
  • Yuichi Sugiyama
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 7)


Drug transporters play indispensable roles in the disposition of drugs in the body; e.g., in hepatic and renal eliminations, intestinal absorption, and in transport across active barriers, and consequently, in the response to drugs. Importance of the solute carrier family, such as OATP/SLCO, OCT/SLC22, OAT/SLC22, and MATE/SLC47, and the ATP-binding cassette transporters, such as P-glycoprotein/ABCB1, MRPs/ABCC, and BCRP/ABCG2, are well recognized in drug discovery and clinical situations. To date, it is however a great challenge to identify in vivo probe substrates and inhibitors applicable for investigating the impact of drug transporters in humans. This chapter has summarized the relevant clinical drug–drug interaction and pharmagenomic studies on drug transporters in humans, as well as some in vitro studies on transporters, in order to suggest applicable probe substrates and inhibitors for drug transporters. In addition to the drugs at the market, some endogenous and food-derived metabolites are probes for drug transporters. This chapter also highlights the impact of drug transporters on such compounds.


Drug Transporter Breast Cancer Resistance Protein Probe Substrate Clearance Ratio Positron Emission Tomography Probe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



ATP-binding cassette


Area under the plasma concentration–time curve


Blood–brain barrier


Breast cancer resistance protein


Overall intrinsic clearance


Renal clearance


Total body clearance


Central nervous system


Clearance ratio (ratio of renal clearance to the glomerular filtration)


Drug–drug interaction


Hepatic availability


Unbound fraction in plasma


Glomerular filtration rate


Mutlidrug and toxic compound extrusion


Multidrug-resistant associated protein




Sodium bile acid co-transporting polypeptide


Organic anion transporter


Organic anion transporting polypeptide


Organic cation transporter


Positron emission tomography




The clearance for the back flux


The clearance for the influx


Relative activity factor


Solute carrier


Single nucleotide polymorphism


Single photon emission computed tomography


Tetraethyl ammonium


(15R)-16-m-tolyl-17, 18, 19, 20-tetranorisocarbacyclin



The authors would like to thank Dr. Mari Miyajiam and Sumito Ito for their kind support.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hiroyuki Kusuhara
    • 1
  • Kenta Yoshida
    • 1
  • Yuichi Sugiyama
    • 1
    • 2
  1. 1.Graduate School of Pharmaceutical SciencesThe University of TokyoTokyoJapan
  2. 2.Sugiyama LaboratoryRIKEN Innovation Center, RIKEN Research Cluster for Innovation, RIKENTsurumi-ku, YokohamaJapan

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