Comparative diffusion of drugs through bronchial tissue

• Published in: International journal of pharmaceutics Vol. 357; no. 1; pp. 32 - 36
• Main Authors: van Zyl, Johann M., Derendinger, Brigitta, Seifart, Heiner I., Van der Bijl, Pieter
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.06.2008; Elsevier
• Subjects: Albuterol - metabolism; Animals; Biological and medical sciences; Bronchi - metabolism; Bronchial tissue; Bronchodilator Agents - chemistry; Bronchodilator Agents - metabolism; Chromatography, High Pressure Liquid; Diffusion; General pharmacology; In Vitro Techniques; Ipratropium - metabolism; Ipratropium bromide; Kinetics; Mass Spectrometry; Medical sciences; Methylxanthines; Perfusion; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Salbutamol; Structure-Activity Relationship; Swine; Xanthines - metabolism; Salbutamol; Bronchial tissue; Methylxanthines; Permeability; Ipratropium bromide; Drug; Agonist; Pharmaceutical technology; Bronchodilator; β2-Adrenergic receptor; β-Adrenergic receptor agonist; Quaternary ammonium compound; Tissue; Anticholinergic agent; Cholinergic receptor; Muscarinic receptor; Antagonist; Diffusion
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2008.01.028

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.