January 23, 2021
Authors Michael J Dolton1, Po-Chang Chiang2, Fang Ma3, Jin Y Jin4, Yuan Chen3
Affiliations 1 Roche Products Australia, Level 8/30-34 Hickson Road, Millers Point NSW 2000 Australia. 2 Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA. 3 Drug Metabolism and Pharmacokinetics, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA. 4 Clinical Pharmacology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080 USA.
Presentation type Oral
Presenters Michael Dolton
Introduction: Vismodegib displays unique pharmacokinetic characteristics including saturable plasma protein binding to alpha-1 acid glycoprotein (AAG) and apparent time-dependent bioavailability leading to non-linear PK with dose and time, significantly faster time to steady-state and lower than predicted accumulation. Objectives: Given these unique characteristics, a PBPK model was developed to explore mechanistic insights into saturable protein […]