Scientific Publications by FDA Staff

Expert Opin Drug Discov 2020 May;15(5):539-49

Advances in cell-based permeability assays to screen drugs for intestinal absorption.

Volpe DA

INTRODUCTION: Successful oral therapy requires sufficient intestinal absorption to enable the drug to reach its site of action. Evaluation of intestinal permeability is important for candidate selection during drug discovery and development. In vitro cell assays that correlate with human intestinal absorption serve as an alternative to more expensive and low-throughput preclinical or clinical in vivo methods to investigate a drug's intestinal permeability. AREAS COVERED: This article focuses on cell-based models utilized to predict in vivo intestinal drug permeability. This includes the utilization of the Caco-2 and other cell epithelial lines, human primary intestinal cells, and induced pluripotent stem cells. Additional topics include co-cultures, three-dimensional models, and microfluidic systems. EXPERT OPINION: In vitro permeability assays are utilized to predict a drug's permeability class or intestinal fraction absorbed. Newer Caco-2 co-cultures, intestinal epithelial cells, and three-dimensional models better replicate the architecture of the mucus and multi-cellular epithelium layer. Such models may result in an improved understanding of a drug's intestinal permeability mechanism(s). Nevertheless, these newer models require validation with larger sets of drugs having known intestinal absorption before they can be routinely utilized to estimate human intestinal drug absorption.