Tracheal Barrier and the Permeability of Hydrophilic Drugs and Dipeptides

概要

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The permeability of model hydrophilic compounds with defferent molecular weights and model dipeptides were examined to characterize the tracheal epithelial barrier in in vitro experiments using excised rabbit trachea.6-Carboxyfluorescein (6-CF; 376 Da) and fluorescein isothiocyanate (FITC)-dextrans (FDs) with varying molecular weights (4 to 70 kDa) were used as model hydrophilic and macromolecular compounds, and glycyl-D-phenylalanine (Gly-D-Phe) and glycyl-L-phenylalanine (Gly-L-Phe) were used as model dipeptides in this experiment.The apparent permeability coefficients (P_<app>) of 6-CF and FDs with Mw 376 Da to 70 kDa ranged form 2.35×10^<-7> to 4.05×10^<-10> cm/s and exhibited a good inverse correlation with their molecular weights. The tracheal permeability of 6-CF, FD-4 (4 kDa) and FD-10 (10 kDa) were increased over three fold by 10 mM glycocholate, which is an absorption enhancer. The P_<app> of Gly-D-Phe was 1.03×10^<-6> cm/s and there was no metabolism during tracheal permeation. Gly-L-Phe was immediately degraded in the mucosal fluid and its intact form was not detected in serosal fluid during the 150 min experimental period. These results suggest that absorption of some peptide drugs via the respiratory tract may contribute to their systemic delivery following pulmonary administration by intratracheal insufflation and instillation.
公益社団法人日本薬学会の論文
1999-05-15