In predicting intestinal absorption, which statement is most accurate?

In predicting intestinal absorption, which statement is most accurate?

• A. Caco-2 cell permeability assays are rarely used to predict intestinal absorption.
• B. Caco-2 cell permeability assays are commonly used to predict intestinal absorption, but results can vary between laboratories and may not capture in vivo active transport.
• C. Caco-2 assays measure gastric pH effects.
• D. Caco-2 assays replace animal studies.

Answer: (B)

Caco-2 permeability assays are a widely used in vitro tool to estimate how well a compound can cross the intestinal lining. They use a monolayer of human-derived enterocyte-like cells to measure how quickly a drug moves from the intestinal-facing side to the blood-facing side, providing a permeability value that helps predict oral absorption and inform classifying compounds by permeability. This option is the best because these assays are routinely used to forecast intestinal absorption and guide early drug development. However, results can vary quite a bit from one lab to another due to differences in cell source, passage number, culture conditions, media, and assay setup, all of which affect the measured permeability and apparent efflux. In addition, while Caco-2 cells express several transporters and can reflect some active transport, their transporter expression and regulation do not perfectly match the human intestine, so in vivo active transport may not be fully captured. As a result, Caco-2 data are informative but not definitive and do not replace animal or human studies. They also do not assess gastric pH effects, which occur in the stomach rather than the intestinal epithelium.

Caco-2 permeability assays are a widely used in vitro tool to estimate how well a compound can cross the intestinal lining. They use a monolayer of human-derived enterocyte-like cells to measure how quickly a drug moves from the intestinal-facing side to the blood-facing side, providing a permeability value that helps predict oral absorption and inform classifying compounds by permeability.

This option is the best because these assays are routinely used to forecast intestinal absorption and guide early drug development. However, results can vary quite a bit from one lab to another due to differences in cell source, passage number, culture conditions, media, and assay setup, all of which affect the measured permeability and apparent efflux. In addition, while Caco-2 cells express several transporters and can reflect some active transport, their transporter expression and regulation do not perfectly match the human intestine, so in vivo active transport may not be fully captured. As a result, Caco-2 data are informative but not definitive and do not replace animal or human studies. They also do not assess gastric pH effects, which occur in the stomach rather than the intestinal epithelium.