Permeability & Transporters

Permeability of a drug candidate, often referred to as its capability to penetrate across the human GI tract, is a key factor governing its oral absorption. The permeability of drugs and drug-like molecules across biological membranes is governed by processes that include passive diffusion, active uptake, active efflux and receptor-mediated endocytosis. The potential for drug interaction with these proteins to affect both drug absorption and drug delivery to intracellular organelles may have significant implications for drug design.

The most used approaches to study the permeability of the molecule across the intestinal barrier are cell models such as Caco-2 or MDCK.

Absorption of many compounds is also affected by ATP-driven efflux pumps (efflux transporters, e.g. P-glycoprotein) located on the cell membranes of various tissues in the body. Evaluation of the role of transporter proteins in the absorption process (transporter substrate), and possible interactions related to their functions (transporter inhibition & activation) should be taken account in permeability experiments.

Interactions with drug transporter are important in drug discovery and development, not only for absorption and elimination, but for potential drug-drug interactions as well.