Predicting the intestinal absorption potential of hits and leads

Today's pharma environment requires rapid and reliable methods of screening drug leads for intestinal permeability potential in the early stages of drug discovery. Techniques using excised tissues, Caco-2 cells, artificial membranes, ‘ in silico’ techniques and surface plasmon resonance (SPR)-based biosensors are critically examined in terms of their reliability, measurement criteria, throughput and utility in identifying potentially successful or unsuccessful drug molecules. Han van de Waterbeemd, Christopher Kohl – Pfizer Global Research & Development, Sandwich Laboratories, Pharmacokinetics, Dynamics and Metabolism, Sandwich, Kent, UK CT13 9NJ For convenience of the patient most drugs are being given orally. Therefore, high levels of intestinal absorption are a key goal in most drug discovery projects. The authors Markku Hämäläinen and Asa Frostell-Karlsson have recently developed a new tool to access human oral absorption using surface plasmon resonance. Here, they review in addition some related techniques to assess oral absorption going from excised tissues, Caco-2 cells and artificial membranes to in silico approaches. The appropriate use of each of these techniques either as standalone or in combination depends on the discovery phase as different specifications apply in terms of throughput and costs.