Role of Organic Anionic Transporter (OAT2) in the Hepatic Clearance of Anionic/Zwitterionic Drugs – ‘A missing piece of the puzzle’
Date: February 26 2019
Presenter(s): Manthena V. Varma, M.S., Ph.D.
Summary of the Presentation:
Membrane transporters play a key role in the absorption, distribution, clearance and elimination (ADCE) of drugs. Particular emphasis has been given to hepatic uptake clearance mediated by organic anion transporting polypetides (OATPs), where many high MW acids/zwitterions (i.e., extended clearance classification system class 1A, ECCS 1B/3B drugs) are shown to be substrates. OAT2, a member of solute carrier 22A (SLC22A7), is expressed in liver and kidney; and is known to transport several xenobiotics and endogenous compounds (eg. creatinine and cGMP). Although protein abundance of OAT2 in human liver is relatively similar to other major uptake transporters such as OATP1B, NTCP and OCT1, little is known about its role in the clinical pharmacokinetics of drugs. This webinar will summarize our recent studies providing evidence for the role of OAT2-mediated hepatic uptake in the clearance of low MW acids/zwitterions (ECCS 1A drugs). Application of these learnings in clearance optimization and drug development will be discussed.
Related References:
Kimoto et al., J Pharmacol Exp Ther. 2018:322-334.
Vildhede et al., Mol Pharm. 2018:3227-3235.
Bi et al., Mol Pharm. 2018:1284-1295.
Bi et al., J Pharmacol Exp Ther. 2018:390-398.
Mathialagan et al., Xenobiotica. 2018 Oct;48(10):1037-1049.
About the presenter:
VARMA, Manthena, PhD
Research Fellow, Pfizer Inc. Groton, CT, USA
Biography
Manthena Varma, PhD is Research Fellow, at Pfizer Inc. Dr. Varma received his B. Pharm. degree from the Kakatiya University, Warangal, India; and an M.S. degree (2001) and PhD in Pharmaceutics (2005), from the National Institute of Pharmaceutical Education and research (NIPER), Mohali, India. Later, Dr. Varma worked as a Post Doctoral Fellow at the Department of Pharmaceutics, University of Minnesota (Minneapolis). In 2008, he joined Worldwide R&D, Pfizer, Groton, CT. Dr. Varma holds an Adjunct faculty position in the Department of Pharmacy of the University of Rhode Island. Dr. Varma’s research is focused in the fields of ADME/PK technologies and strategies in drug design and development, role of drug transporters and transporter-enzyme interplay (extended clearance) in ADME/PK, clinical pharmacokinetics and DDI predictions/evaluation via mechanistic (PBPK) modeling. He published about 125 original articles/reviews and presented over 75 presentations at the scientific conferences in these areas.
