Pharmacokinetics-On-a-Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

Abstract

Despite many ongoing efforts across the full spectrum of pharmaceutical and biotech industries, drug development is still a costly undertaking that involves a high risk of failure during clinical trials. Animal models played vital roles in understanding the mechanism of human diseases. However, the use of these models has been a subject of heated debate, particularly due to ethical matters and the inevitable pathophysiological differences between animals and humans. Current in vitro models lack the sufficient functionality and predictivity of human pharmacokinetics and toxicity, therefore, are not capable to fully replace animal models. The recent development of micro-physiological systems has shown great potential as indispensable tools for recapitulating key physiological parameters of humans and providing in vitro methods for predicting the pharmacokinetics and pharmacodynamics in humans. Integration of Absorption, Distribution, Metabolism, and Excretion (ADME) processes within one close in vitro system is a paramount development that would meet important unmet pharmaceutical industry needs. In this review paper, synthesis of the ADME-centered organ-on-a-chip technology is systemically presented from what is achieved to what needs to be done, emphasizing the requirements of in vitro models that meet industrial needs in terms of the structure and functions.