Comparative diffusion of drugs through bronchial tissue
2008
Abstract The purpose of the study was to investigate the molecular diffusion of drugs across porcine bronchial tissue. Using an in vitro flow-through diffusion system, a series of model compounds were tested. These included theophylline, caffeine, theobromine, enprofylline, salbutamol, ipratropium bromide, and trimethoprim. All drugs were assayed by HPLC in conjunction with UV/vis or MS/MS detection. The results indicated that the mean flux value of theophylline was higher than that of all the other drugs listed above. Within the log 10 P range from −2.21 (ipratropium bromide) to 1.364 (trimethoprim), a sigmoidal relationship was found to exist between the apparent permeability coefficients ( P app ) and the octanol/water partition coefficients across the bronchial tissue. The diffusion of ipratropium bromide ( P app 1.6 × 10 −8 cm/s) across bronchial tissue was similar to that of salbutamol ( P app 1.5 × 10 −8 cm/s). The data obtained in this study indicate that although lipophilicity is a main determinant in the diffusion of drug compounds across bronchial tissue, the number and position of alkyl groups also reflect the ability of the latter to cross membrane barriers.
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