Application of biopharmaceutics classification system (BCS) in drug transport studies across human respiratory epithelial cell monolayers

Abstract

Transport studies of model drugs were conducted across the human nasal epithelial (HNE) and normal human bronchial epithelial (NHBE) cell monolayers cultured by air–liquid interface method. Physicochemical properties (e.g., molecular weight, calculated partition coefficient, dose number) of model drugs were quoted from literatures and apparent permeability coefficients (P app) across the HNE and NHBE cell monolayers were directly measured. A linear relationship was observed between the P app values of model drugs in the HNE and NHBE cell monolayers. As the molecular weight of model drugs increased, the P app showed a decreasing pattern while the increase of partition coefficients resulted in the increment of P app. These results indicated that the transport of model drugs across both cell monolayers followed mainly the passive diffusion mechanism, although substrates mediated by drug transporters showed a deviating pattern. It was also interesting to note that almost all model drugs could be grouped into the same biopharmaceutics classification system as that classified by the human intestinal permeability when the P app was plotted as a function of dose number (D 0) of each drug.