Berghausen, Joerg, Petersson, Carl, Zhou, Xin, Cebrian, Brian, Davies, Michael, DeMent, Kevin, Eddershaw, Peter, Emami Riedmaier, Arian, Leblanc, Alix, Manveski, Nenad, Marathe, Punit, Mavroudis, Panteleimon, McDougall, Robin, Parrott, Neil, Reichel, Andreas, Rotter, Charles, Tess, David, Volak, Laurie, Xiao, Guangqing, Yang, Zhen and Baker, James (2022) Current approaches for predicting human PK for small molecule development candidates: Findings from the IQ Human PK Prediction Working Group Survey. The AAPS journal.

Abstract

Accurate prediction of human clearance (CL) and volume of distribution at steady state (Vd,ss) for small molecule drug candidates is an essential component of assessing likely efficacious dose and clinical safety margins. In 2021, the IQ Consortium Human PK Prediction Working Group undertook a survey of IQ member companies to understand the current PK prediction methods being used to estimate these parameters across the pharmaceutical industry.
The survey revealed a heterogeneity in approaches being used across the industry (e.g., use of allometric approaches, differing incorporation of binding terms, and inconsistent use of empirical correction factors for in vitro-in vivo extrapolation, IVIVE), which could lead to different PK predictions with the same input data. Member companies expressed an interest in improving human PK predictions by identifying the most appropriate compound-class specific methods, as determined by physiochemical properties and knowledge of CL pathways. Furthermore, there was consensus that increased understanding of the uncertainty inherent to the compound class-dependent prediction would be invaluable in aiding communication of human PK and dose uncertainty at the time of candidate nomination for development.
The human PK Prediction Working Group is utilizing these survey findings to help interrogate clinical IV datasets from across the IQ consortium member companies to understand PK prediction accuracy and uncertainty from preclinical datasets.

Item Type:	Article
Keywords:	Human PK prediction, Clearance, Volume of distribution, Uncertainty, IQ Consortium
Date Deposited:	04 Aug 2022 00:45
Last Modified:	04 Aug 2022 00:45
URI:	https://oak.novartis.com/id/eprint/47406