Mettler, Lina, Riede, Julia, Huth, Felix, Lohasz, Christian, Loskill, Peter and Poller, Birk (2026) Navigating ADME Profiling Challenges in Microphysiological Systems: Evaluation of a Liver-Chip Model for Clearance Prediction. Journal of pharmaceutical sciences.

Abstract

Accurate prediction of hepatic clearance is essential for drug development, yet conventional in vitro models often fail to replicate the complexity of human liver physiology, particularly for low-clearance compounds. This study evaluates a commercially available liver-chip model featuring a two-compartment microfluidic architecture that supports co-culture of primary human hepatocytes and liver sinusoidal endothelial cells. A panel of 15 drugs with diverse metabolic pathways and clearance rates was tested to assess the model’s predictive performance. Key system parameters - including compound permeability, non-specific binding, and evaporation - were systematically characterized to optimize assay conditions. While high-clearance compounds were underpredicted, model showed better performance for more metabolically stable drugs. After correction, more than 79% of predictions fell within a threefold range of observed human values. The liver-chip meets key criteria for ADME applications and offers practical advantages for long-term studies, though further refinement is needed to enhance quantitative accuracy across the full clearance spectrum.

Item Type:	Article
Keywords:	Absorption, Distribution, Metabolism, and Excretion (ADME), Drug metabolizing enzyme(s), Hepatic clearance In Vitro/In Vivo (IVIVC) Correlation In vitro model
Date Deposited:	28 Mar 2026 00:45
Last Modified:	28 Mar 2026 00:45
URI:	https://oak.novartis.com/id/eprint/59085