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Webinar: Incorporating transporter kinetics into PBPK models
December 1, 2016 @ 8:00 am - 9:00 am
The importance of transporter effects on drug absorption, disposition, clearance, and drug-drug interactions has gained considerable attention over the past few years. Significant progress has been made in identifying the gaps in knowledge about the role of transporters in drug disposition. Lack of data on absolute expression levels of transporters in various tissues, as well as our ability to relate those expressions to drug-specific in vitro data, are frequently indicated as primary reasons behind our inability to reliably predict the in vivo exposure of drugs whose disposition is dependent on interactions with transporters. Research investments in this area have resulted in a large number of recent publications focused on quantifying the transporter mRNA and/or protein levels in various tissues in different species.
One of the previous webinars in this series discussed transporters affecting drug absorption. This webinar will focus more on transporters involved in drug distribution and elimination. A brief summary of current information on transporter expression levels will be followed by a description of options for including transporters in the GastroPlus™ PBPK model. The importance of interplay between transporter-mediated secretion and metabolism of a compound, and how it may affect the successful in vitro-in vivo extrapolation of metabolic clearance, will be discussed. Finally, we will present an example of PBPK model development and subsequent prediction of pharmacokinetics in a pediatric population for a compound eliminated primarily via transporter-mediated secretion.
Viera Lukacova, Ph.D.
Team Leader – Simulation Technologies
Simulations Plus, Inc.