Albumin-Mediated Uptake of Highly Bound Anionic Drugs by Hepatic and Renal Transporters: A Real Phenomenon or an in vitro Artifact? |Ms. Mengyue (Melody) Yin & Mr. Shawn Pei Feng Tan
This webinar aims to highlight current knowledge about albumin-mediated uptake by organic anion transporters expressed in liver and kidney. Special emphasis will be placed on in vitro evidence to support the hypothesis and the complexity confounded by the non-specific binding of the drug-albumin complex. Possible implications to improve the prediction of transporter-mediated hepatic and renal clearance for highly protein bound drugs will be discussed.
Plasma proteins or human serum albumin have been reported to increase the in vitro uptake clearance of highly albumin-bound anionic drugs. Various hypothesis and mechanistic models have been proposed to explain such phenomenon. However, some controversial observations have suggested that possible artifact of the non-specific binding may complicate the data interpretation. This special webinar will be started with two presentations given by the graduate students (their works were presented at the 2022 International ISSX meeting as poster presentations), followed by a panel discussion with all speakers, their scientific mentors, and international renowned experts in transporter field. The knowledge gained from this presentation will help scientists at all levels to learn the concept of albumin-mediated uptake effects by transporters; understand their complexity and current knowledge gaps. The discussion will also provide some insights and practical considerations on designing in vitro transport kinetic studies for highly protein bound drugs to improve their in vitro to in vivo extrapolation.
Speakers: Mengyue (Melody) Yin, University of Washington, USA Shawn Pei Feng Tan, University of Manchester, UK
Panelists: Aleksandra Galetin, University of Manchester, UK Jash Unadkat , University of Washington, USA Yuichi Sugiyama, Josai International University, Japan