ADME WorkBench Status, Plans, Current Applications (What’s New?) September 17, 2013 Conrad Housand

Agenda Introduction –We intend for this to become a monthly user’s group meeting (but non-users are welcome to attend) –We’ll review newly added features from the previous month –We’ll describe the status of features currently in development, and their estimated availability date –We’ll talk about upcoming events –We’ll present user research and applications –We’ll listen to feedback from customers and the ADME community

New Features Gut metabolism –Scale from intestinal microsomes (linear/saturable) –Scale from liver microsomes (linear/saturable) Gut transporters –Influx/efflux based in total microsomal abundance (linear/saturable) –Influx/efflux based on microsomal abundance relative to illeum/Caco2 (linear/saturable)

New Features Saturable renal clearance –Tubular secretion/reabsorption Externally-defined absorption rate –Imported tabular absorption rate vs. time data User-defined model parameters –Additions to user interface and project database –Provides “hook” to custom code in PBPK model

In Development Additional target species –Rabbit, monkey, guinea pig User-defined PBPK tissues –User-specified physiological parameters Variability –Basic physiological parameters Age dependence –Basic physiological parameters, some metabolism

In Development Advanced inhalation model –Gloede + additions for particulate deposition and dissolution Metabolites –Parallel PBPK models to track parents/metabolites –Metabolism in multiple tissues: gut, liver to start

In Development Examples –Midazolam w/ transporters Dermal absorption –Externally-supplied flux –Thanks to John Troutman, P&G

In Development Next webinar in October – – –October 22: –October 24:

Thank you Questions? Thank you!