Rapid permeability screening in drug discovery to predict human intestinal absorption.

After oral administration of a drug, several hurdles have to be passed before the drug becomes systemically available. First of all, the drug has to be liberated from the pharmaceutical formulation. Within the gastrointestinal (GI) tract, the drug has to be resistant to enzymes and different pH environments. The dissolved compound has to be absorbed through the intestinal cell layer, which means it has to traverse many barriers formed by cell membranes. These cell membranes are composed of phospholipid bilayers, which are oily barriers that hinder the passage of charged or hydrophilic molecules. After absorption from the intestinal tract, the compound can reach the systemic blood stream via the portal vein through the liver. First pass metabolism in the intestine and in the liver and biliary excretion can limit the systemic availability.