Human intestinal permeability

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Biopharmaceutics
• Translational Medicine

Background:

• Accurate prediction of drug absorption is crucial for effective drug development.
• Human effective permeability (Peff) is a key parameter in assessing drug absorption.
• Preclinical models are often used to predict human drug behavior, but their accuracy varies.

Purpose of the Study:

• To review and validate human effective permeability (Peff) measurements.
• To compare human Peff values with data from preclinical transport models.
• To assess the predictability of human in vivo permeabilities using preclinical models.

Main Methods:

• Review of human jejunal perfusion techniques and Peff measurements.
• Comparison of human Peff with data from rat jejunum perfusion, Caco-2, and Ussing chamber models.
• Analysis of correlations between measured human Peff and pharmacokinetic data.

Main Results:

• Human Peff values show a strong correlation with drug absorption extent and pharmacokinetic profiles.
• Preclinical models, particularly for passively transported compounds, can predict human in vivo permeabilities with high accuracy.
• Carrier-mediated transport requires special consideration and scaling factors for accurate prediction.

Conclusions:

• Human Peff measurements are reliable predictors of oral drug absorption.
• Preclinical models offer valuable insights into human drug permeability, with caveats for carrier-mediated transport.
• Further clinical studies are needed to elucidate in vivo factors influencing drug transport and bioavailability, including MDR and metabolism.