title: Comparative diffusion of drugs through bronchial tissue.
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 log10P range from -2.21 (ipratropium bromide) to 1.364 (trimethoprim), a sigmoidal relationship was found to exist between the apparent permeability coefficients (Papp) and the octanol/water partition coefficients across the bronchial tissue. The diffusion of ipratropium bromide (Papp 1.6 x 10(-8)cm/s) across bronchial tissue was similar to that of salbutamol (Papp 1.5 x 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.
authors.affiliation: Division of Pharmacology, Department of Medicine, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa. jmvzyl@sun.ac.za
authors.forename: Johann M
authors.initials: JM
authors.lastname: van Zyl
authors.forename: Brigitta
authors.initials: B
authors.lastname: Derendinger
authors.forename: Heiner I
authors.initials: HI
authors.lastname: Seifart
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Bijl
mesh_terms: D000420:Albuterol / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D066298:In Vitro Techniques; D009241:Ipratropium / Q000378:metabolism; D007700:Kinetics; D013058:Mass Spectrometry; D010477:Perfusion; D013329:Structure-Activity Relationship; D013552:Swine; D014970:Xanthines / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D014970:Xanthines; D009241:Ipratropium; D000420:Albuterol