pH-SPECIFIC PREDICTION MODELS FOR MEMBRANE PERMEABILITY

Approved drugs include about 85% of ionisable compounds. Majority of drug-related properties in the early stage of drug research are measured at the neutral pH, while properties of ionisable compounds depend on the pH of the environment. The pH range in gastrointestinal tract varies in the large scale (from pH ~2 to ~9) and therefore influences human intestinal absorption. The robust experimental method to analyse pH influence to human intestinal absorption is the parallel artificial membrane permeability assay (PAMPA). So far pH-profiles of membrane permeability have not been studied in detail. Ignoring analysis of pH-profiles of membrane permeability may lead to false conclusions during discovery of new active compound and cause retraction of potential new drug candidates in the late development phase.