In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment

Research Overview

Proarrhythmic cardiotoxicity blocks drug development and threatens patients, and stem cell-based new approach methodologies are increasingly proposed to replace models that fail to capture human cardiac electrophysiology.

This study expanded a 3D human cardiac microtissue model into quantitative risk assessment by coupling it with a physiologically based pharmacokinetic model — allowing potentially harmful concentrations predicted in vitro to be compared directly against in vivo therapeutic levels, and yielding concentration responses and margins of exposure for physiologically relevant compounds.