Scope

Quantitative information on expression of drug transporters in human tissues (e.g. liver, intestine, kidneys) is crucial for in vitro to in vivo prediction of transporter-mediated drug disposition (including inter-individual variability) using physiological-based pharmacokinetic models (PBPK).

Since inception, we have completed the following research (for publications, see the publication page):

Year 1 (April 2012-13):

  1. Quantified the interindividual protein expression of OATP1B1, OATP2B1, OATP1B3, MDR1, BCRP, and MRP2 in the UW Liver Bank (n=~60).
  2. Determined if the expression of the above transporters is correlated with donor age or sex, genotype of the transporter, or with each other.
  3. Determined the expression of the above transporters in cell lines/tissues provided by the sponsors (n=20 each).

Year 2 (April 2013-14):

  1. Quantified the activity/expression correlation of transporters in transfected cell lines such as OATP1B1 and BCRP.
  2. Quantified protein levels of BSEP, MATE1, MRP3, MRP4, NTCP and OCT1 in the UW Liver Bank and determined whether the expression of the above transporters is correlated with donor age or sex, genotype of the transporter or with each other.
  3. Quantified protein levels of major hepatobiliary transporters, namely, Bcrp, Bsep, Mdr1, Mrp2, Mrp3, Mrp4, Ntcp, Oatps, and Oct1 in liver tissues and unplated cryopreserved hepatocytes from male beagle dogs, cynomolgus monkeys, and Sprague-Dawley/Wistar rats and compared the expression of human hepatic transporters with those in these animal species.
  4. Determined the expression of the human transporter in cell lines/tissues provided by the sponsors (n=20 each).

Year 3 (April 2014-15), the following research is ongoing:

  1. To quantify major hepatobiliary transporters, including BCRP, BSEP, MATE1, MDR1, MRP2, MRP3, MRP4, NTCP OATPs (OATP1B1, OATP1B3, OATP2B1), and OCT1 in pediatric livers.
  2. To identify source of diseased human tissue (e.g. liver or kidney failure) for future work.