The Caco-2 cell monolayer: usefulness and limitations

Abstract

Background: The Caco-2 monolayer has been used extensively for the high-throughput screening of drug permeability and identification of substrates, inhibitors, and inducers of intestinal transporters, especially P-glycoprotein (P-gp). Traditionally, the Caco-2 monolayer is viewed as a single barrier rather than a polarized cell monolayer consisting of metabolic enzymes that are sandwiched between two membrane barriers with distinctly different transporters. Objective: This review addressed the usefulness and limitations of the Caco-2 cell monolayer in drug discovery and mechanistic studies. Methods: This mini-review covered applications of the Caco-2 monolayer, clarified misconceptions, and critically addressed issues on data interpretation. Conclusion: The catenary model extends the usefulness of Caco-2 monolayer and provides proper mechanistic insight and data interpretation.

Keywords::

• Caco-2
• catenary model
• efflux ratio
• inducer
• induction
• inhibition
• inhibitor
• kinetic modeling
• permeability
• P-glycoprotein
• single-barrier model
• substrate

Notes