PET imaging and pharmacokinetic modelling of hepatobiliary Transporters
Date: Tuesday December 11 2018
4pm to 5pm
Venue: Ground floor seminar room G10, 70 Symonds St
A Bioengineering seminar by Professor Yuichi Sugiyama, RIKEN Cluster for Science, RIKEN, Yokohama, Japan.
Abstract: The changes in pharmacokinetics due to genetic polymorphisms and drug-drug interactions involving transporters can often have an adverse effect on the therapeutic safety and efficacy of many drugs. For drugs with intracellular target molecules, cellular efflux transporters are the determinant of pharmacological effect or adverse reactions even though they have negligible impact on the plasma concentrations. Because of difficulty in quantitative evaluation of the efflux process, the role of efflux transporters remains unclear in humans.
In order to elucidate the quantitative relationship between the transport activities and drug response, labeled PET probes are being developed for specific transporters. In this presentation, I will show you our recent progress in the analysis of plasma clearance of drugs and PET imaging to evaluate the transporter function in vivo including PET probes for hepatic uptake transporters (OATP1B1, OATP1B3) and biliary excretion transporters (MRP2, BCRP)) both in experimental animals and in human.
Elucidation of the rate-determining process in the overall hepatic elimination of drugs is therefore critical for predicting their hepatic clearance, and their systemic and regional exposures. I will show how to understand the so-called “Extended clearance concept” and to establish a physiologically based pharmacokinetic (PBPK) model that includes the transporter-mediated membrane transport and enzyme-mediated metabolism processes and to investigate the effect of changes in transporter (influx, efflux) function and metabolizing enzyme function on the pharmacokinetics of drugs in the blood and the liver and, ultimately, the pharmacological and/or toxicological effects.
Music by Joakim Karud [ Ссылка ]
