STANDARDIZATION OF IN VITRO DRUG PERMEABILITY IN CACO-2 STUDY AND THEIR CORRELATION TO HUMAN DATA IN VIVO

Inter-laboratory or inter-membrane variations in drug permeability across Caco-2 monolayers are considered to be one of the most critical problems in drug absorption screening performed in pharmaceutical companies. We have already reported that the variations in drug permeability found in Caco-2 or MDCK monolayers are basically due to the differences in the paracellular permeability through cell junctions. In this paper, paracellular permeability of various drugs was calculated according to the pore-theory proposed by Renkin1), then their permeability to the standard membrane having the defined pore size of the paracellular pathway was re-calculated. Through this mathematical correction process, inter-laboratory or inter-membrane variations in drug permeability could be minimized, giving the standardized permeability of all drugs. The experimental conditions such as pH of the transport medium influence the permeability of weak-electrolyte drugs2). Assuming that the pH of the apical medium mainly affects the transcellular transport of drugs, drug permeability of defined pH condition was estimated from the concentration of unionized molecule of drugs. The results obtained in this research are quite important to predict the oral drug absorption in humans from the in vitro study with Caco-2 or other cell monolayers.