Challenges in Predicting PK for Transporter Substrates

Xiaomin Liang, Ph.D., is a Senior Scientist II in the Department of Drug Metabolism at Gilead Sciences Inc. She obtained her B.S. degree in molecular toxicology from the University of California, Berkeley in 2011, and her Ph.D. degree in pharmaceutical sciences with a focus on membrane transporters, transporter-mediated drug disposition, and pharmacokinetics (PK) from the University of California, San Francisco in 2016. Following a brief fellowship at the Office of Clinical Pharmacology at the FDA, she joined Gilead in 2017. Her primary research interests are in the applications of transporter biology, in vitro methodologies, and mechanism-based PK/PBPK modeling to understand the ADME of compounds and translate preclinical data to predict human PK.

Dr. Ying-Hong Wang is a senior reviewer in the Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences (OTS)/CDER. Prior to joining the FDA, she worked for 14 years at Merck, where she was responsible for preclinical and clinical development of numerous compounds in multiple therapeutic areas. She chaired the Quantitative Prediction of Drug Interaction Working Group and developed the internal guidelines for DDI prediction. Her modeling work on predicting and characterizing enzyme and transporter-mediated DDI and hepatic impairment contributed to the NDA approvals of grazoprevir/elbasvir and letermovir. Dr. Wang earned her Ph.D. from the Oregon Health Science University and completed her Clinical Pharmacology Fellowship training at the Indiana University-Purdue University Indianapolis. Her current research focuses on applications of PBPK modeling in CYP induction, transporter-mediated DDI, and hepatic impairment.

Kunal Taskar, Ph.D., is currently working as Director, Global Head of PBPK Modelling at GSK. Kunal completed his doctorate more than a decade ago and postdoctoral research at Texas Tech University Health Sciences department, USA, in Quentin Smith’s lab with research focused on Neuropharmacokinetics and role of transporters in drug delivery across the blood-brain barrier (BBB).

Kunal’s experience and research focus include: PBPK modeling of small/large molecules and new modalities for PK and dose predictions, drug-drug interaction predictions and mechanistic understanding of the clinically occurring drug–drug interactions; and application of PBPK modeling in special populations including pediatrics, pregnancy, and organ impairment. His expertise also includes transporter mediated drug delivery and intracellular drug concentrations, especially the role of uptake and efflux transporters in drug pharmacokinetics-pharmacodynamics in disease and toxicology; novel transporters and role in drug disposition and use of endogenous probes and modeling for drug mediated transporter modulations.

Kunal is a member of American Society of Clinical Pharmacology and Therapeutics (ASCPT), International Society for the Study of Xenobiotics (ISSX) and the International Brain Barriers Society. Kunal is a member of several IQ consortiums including MIDD Pilot Program WG, Transporters, Induction PBPK and Pediatric PBPK. He is the founder member and Chair of the ASCPT QP PBPK Community. He received the 2014 AAPS Pharmaceutical Research Meritorious Manuscript Award for a manuscript that was published in the same journal in 2012. He has actively published and given invited talks and conducted workshops at international conferences.

Christine Bowman is a Principal Scientist in the Drug Metabolism and Pharmacokinetics Department at Genentech, Inc.  She is a DMPK project lead for discovery and development projects and her research interests include improving in vitro to in vivo extrapolation with new in vitro methods and PBPK modeling, with a specific focus on transporters.  Prior to joining Genentech, Christine received her PhD from the University of California, San Francisco under Dr. Leslie Benet.

Dr. Xiaoyan Chu is a Senior Director in the Department of Pharmacokinetics, Dynamics, Metabolism, and Bioanalytics at Merck & Co., Inc. in West Point, PA, USA. She obtained her PhD from the Department of Molecular Pharmacokinetics at the Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. After completing her post-doctoral research at the Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan., she joined the Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism at Merck & Co., Inc.   As the leader for the Transporter Science Group, her main responsibilities are to develop transporter related research and operational strategies to support Merck’s discovery and development portfolio, and to evaluate and establish new technologies and approaches to study the role of transporters in pharmacokinetics, efficacy, and toxicity of drugs. She has authored over 80 peer-reviewed research papers, book chapters, and has been invited to speak at over 40 national/international scientific conferences.  She is the member of the International Transport Consortium (ITC) and serves as the Chair of the ISSX Transporter Focus Group from 2019 to 2022. She is also a member of the Editorial Board of Drug Metabolism & Disposition (DMD) and serves on the Industry Advisory Board at the College of Pharmacy & Pharmaceutical Sciences, Washington State University.

Dr. Bridget Morse is currently a Senior Director in PK/PD and scientific lead of Quantitative Clinical Pharmacology at Lilly Research Laboratories. She received her Pharm.D. from Butler University and her Ph.D. in Pharmaceutical Sciences from the University at Buffalo. Bridget has served in the pharmaceutical industry for 10 years as a subject matter expert in pharmacokinetics, transporters, clinical pharmacology and drug-drug interactions, particularly in the use of modeling for substrates of hepatic transporters. She chaired the IQ OATP1B Biomarkers Working Group from 2020-2023, is current Chair of the AAPS Drug Transporter Community and sits on the Editorial Advisory Board for the AAPS Journal. She has over 30 published journal articles and co-authors a recurring book chapter on drug transporters in Foye’s Principles of Medicinal Chemistry.

Dr. Manthena Varma, PhD is Research Fellow, at Pfizer Inc, Groton, CT. Dr. Varma received his B. Pharm. degree from the Kakatiya University, India, and an M.S. degree and PhD in Pharmaceutics, from the National Institute of Pharmaceutical Education and research (NIPER), Punjab, India.  Later, Dr. Varma worked as a Post Doctoral Fellow at the Department of Pharmaceutics, University of Minnesota (Minneapolis). Dr. Varma holds an Adjunct faculty position in the Department of Pharmacy at the University of Rhode Island. His research focus include ADME/PK technologies and strategies in drug discovery and development, role of drug transporters and transporter-enzyme interplay (extended clearance) in ADME/PK, clinical pharmacokinetics and DDI predictions via mechanistic (PBPK) modeling. Varma supported preclinical and clinical development of several Pfizer compounds in the oncology, diabetes, and in NAFLD/obesity areas. He published about 150 original articles/reviews on a variety of ADME/PK topics.