Computational pharmacokinetic modeling of organ-on-chip devices and microphysiological systems

Abstract The current drug discovery and development process involves costly, slow, and risk-laden preclinical in vitro and animal studies and semiempirical protocols for extrapolation of preclinical data to humans. Because of considerable differences in anatomy and physiology between animals and humans, direct extrapolation from animals to human remains very controversial. Similarly, in vitro static cell culture methods cannot mimic the complex in vivo biological and physiological microenvironments. Microfluidics-enabled cell culture technologies paved the way for organ-on-a-chip (OoC) devices and their linking created the prospect for human-on-a-chip systems that emulate in vivo physiological functions and pharmacological responses. Most OoC devices have been designed by trial and error. Advanced physics- and biology-based computational models are required for designing these systems, analyzing experimental data, and translating in vitro data to human responses. This chapter reviews recent achievements and identifies new directions for application of multiscale computational methods in OoC research.