Prolonged airway activity and improved selectivity of budesonide possibly due to esterification

We addressed the question of whether the prolonged local retention of the g lucocorticoid (GC) budesonide (BUD) within airway tissue, due to reversible fatty acid esterification, is associated with protracted topical anti-infl ammatory activity and improved airway selectivity, when compared with fluti casone propionate (FP). BUD or FP at 25 nmol/kg was administered intratrach eally or subcutaneously to adrenalectomized rats, followed by lipopolysacch aride (LPS) intratracheal instillation. The trachea and main bronchi were l avaged 6 h after LPS, and tumor necrosis factor-alpha (TNF-alpha) concentra tion and cell number in the lavage fluid were measured. Instilled 1 h befor e LPS, both GCs reduced TNF-alpha by 70% (p < 0.05) and mononuclear cells b y 55% (p < 0.01), with no reduction in neutrophils. Instilled 6 h before LP S, a significant reduction of TNF-alpha (59%, p < 0.02) and mononuclear cel ls (47%, p < 0.05) was achieved only with BUD. After subcutaneous administr ation, no significant effects were observed. BUD did not exert higher syste mic activity than FP, measured as plasma corticosterone suppression. In con clusion, BUD exerted a more prolonged topical anti-inflammatory activity, a nd a higher airway selectivity than FP, possibly because of its reversible fatty acid esterification within airway tissue. This may contribute to the high efficacy and safety of BUD in asthma, even with once-daily inhalation.