Studying Metabolism with Multi-Organ Chips: New Tools for Disease Modelling, Pharmacokinetics and Pharmacodynamics

Abstract

The intestinal epithelial cells have a large surface area for absorption and metabolism, and the ability to regenerate, thus maintaining intestinal function. These include organ-specific PK aspects such as absorption in the gut, partitioning of the drug into adipose tissue, liver metabolism of the drug or excretion of the drug in the kidney. The usage of automated robotic systems to study metabolism in multiple organ models has recently been proposed by Novak et al. Carbohydrate and protein metabolism was captured in a study by Maass et al., who monitored gut, liver and cardiac OoCs over a period of one week in order to gauge nutrient consumption and metabolic profiles. Metabolic diseases represent a spectrum of disorders ranging from obesity, coronary artery disease, cardiovascular diseases, non-alcoholic fatty liver disease [NAFLD] and type 2 diabetes. Mechanistic toxicology is the identification and understanding of the cellular, biochemical and molecular mechanisms by which chemicals or drugs exert toxic effects.