Pharmacokinetic and pharmacodynamic insights from microfluidic intestine-on-a-chip models

Abstract

Introduction: After administration, a drug undergoes absorption, distribution, metabolism, and elimination (ADME) before exerting its effect on the body. The combination of these process yields the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of a drug. Although accurate prediction of PK and PD profiles is essential for drug development, conventional in vitro models are limited by their lack of physiological relevance. Recently, microtechnology-based in vitro model systems, termed 'organ-on-a-chip,' have emerged as a potential solution. Areas covered: Orally administered drugs are absorbed through the intestinal wall and transported to the liver before entering systemic circulation, which plays an important role in the PK and PD profiles. Recently developed, chip-based in vitro models can be useful models for simulating such processes and will be covered in this paper. Expert opinion: The potential of intestine-on-a-chip models combined with conventional PK-PD modeling has been demonstrated with promising preliminary results. However, there are several challenges to overcome. Development of the intestinal wall, integration of the gut microbiome, and the provision of an intestine-specific environment must be achieved to realize in vivo-like intestinal model and enhance the efficiency of drug development.