TOPICAL ANTI-INFLAMMATORY ACTIVITY OF THE GLUCOCORTICOID BUDESONIDE ON AIRWAY MUCOSA - EVIDENCE FOR A HIT AND RUN TYPE OF ACTIVITY

1. The increase of macromolecular leakage from the airway mucosa into the airway lumen can be significantly counteracted by locally applied BUD 4 μg/kg. 2. The same dose of 4 μg/kg, when administered via intravenous route or to distal trachea and bronchi, is without effect on BRAD-induced leakage. 3. (1)-(2) imply that tracheally applied BUD exerts its anti-permability effect, at such a low dose, strictly at application site and does not act by the part available to the systemic or pulmonary-bronchial circulation. Probably, it influences directly tracheal epithelial lining and affects endothelium of tracheal postcapillary venules. 4. The anti-permeability action is not reproduced by 10 min superfusion with progesterone 3×10-6M, supporting a selective GCS mechanism by topical BUD. 5. Our results suggest that inhalation of selected GCS will lead to a rapidly triggered but protracted anti-inflammatory action on airway mucosa. After triggering, the GCS can be absorbed and inactivated through biotransformation ("hit and run" type of activity). 6. The presented rat tracheal model permits the continuous and precise (area, time) topical application of drugs to airway mucosa. Permeability studies can then be performed on the same airway segment. © 1990 Birkhäuser Verlag.