Date: October 06 2021
Presenter(s): Manthena Varma, PhD
Summary of the presentation:
Breast cancer resistance protein (BCRP; ABCG2) is an ATP-binding cassette efflux transporter expressed in the apical membrane of the small intestine and liver canalicular membrane and plays a key role in the oral absorption and hepatic elimination of substrate drugs. Furthermore, BCRP was suggested to be an important loci of drug-drug interactions (DDIs) in humans. Regulatory guidance from agencies including European Medical Agency (EMA), the Pharmaceuticals and Medical Devices Agency (PMDA, Japan), and United States Food and Drug Administration (USFDA) now recommend appropriate in vitro and/or in vivo assessment of investigational drugs for potential to inhibit several drug transporters including BCRP. Quantitative assessment of DDIs involving BCRP inhibition is challenged by overlapping substrate/inhibitor specificity. This presentation summarizes our recent work assessing in vitro data-informed static model predictions and PBPK modeling to delineate the effects of inhibitor drugs on BCRP- and organic anion transporting polypeptide (OATP)1B-mediated disposition of rosuvastatin, which is a recommended BCRP clinical probe. Leveraging the collective learnings from the static analysis and PBPK modeling and simulations, a strategy to enable BCRP DDI risk assessment will be discussed with case examples.
About the presenter:
Research Fellow, Pfizer Inc. Groton, CT, USA
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.