Host: The 93rd Annual Meeting of the Japanese Pharmacological Society
Name : The 93rd Annual Meeting of the Japanese Pharmacological Society
Number : 93
Location : Yokohama
Date : March 16, 2020 - March 18, 2020
Recently, many studies on genetic polymorphisms (PGx) in drug transporters and transporter-mediated drug-drug interactions(DDI) have been published, and these are part of mechanisms of interindividual difference in drug response. It is important to predict such interindividual difference at early stage of drug development. With a PBPK model, the effect of changes in transporter function on the Pharmacokinetics (PK),and, ultimately, the Pharmacodynamics (PD) and/or Toxicodynamics (TD) will be predicted. I will focus on the following subjects. Recent reports provided quantitative predictions for OATP1Bs-mediated DDIs between statins and cyclosporine A(CsA)/rifampicin(RIF) based on PBPK models. In the process of the analyses, the in vitro–in vivo discrepancies in the Ki values for OATPs were suggested. I will share with you our approach to make the bottom-up prediction possible. Finally, it should be also challenging to reproduce the inter-individual variabilities by considering the mean value and deviation of each PK parameter in a certain population with PBPK model (so-called "virtual clinical study").
