The anti-inflammatory profile of fluticasone propionate.
Fluticasone propionate is a new corticosteroid based on the androstane nucleus. It is more lipophilic than beclomethasone dipropionate (BDP) and budesonide, and binds more avidly to human lung tissue. It has an absolute affinity (KD) of 0.5 nM for the glucocorticoid receptor and a relative receptor affinity 1.5- and 3.0-times greater than that of beclomethasone-17-monopropionate (17-BMP) and budesonide, respectively. The rate of association with the receptor is faster and the rate of dissociation slower than with standard corticosteroids. As a result, the half-life of the corticosteroid-receptor complex is > 10 h. Fluticasone propionate is also highly selective for the glucocorticoid receptor, with little or no activity at other steroid receptors. Pretreatment with fluticasone propionate significantly inhibits the increase in mast cell numbers in the nasal mucosa of rats chronically exposed to toluene di-isocyanate (TDI), and suppresses TDI-induced mast cell degranulation. It is more potent in vitro than dexamethasone, BDP and budesonide in inhibiting anti-CD3-induced human T-lymphocyte proliferation, in attenuating tumour necrosis factor-alpha-induced endothelial cell adhesion molecule expression, and in increasing secretory leucocyte protease inhibitor levels in airway epithelial cells. It is also more potent and longer-acting than other corticosteroids in inhibiting oedema formation, interleukin-5 (IL-5)-induced blood eosinophilia, and IL-5- or platelet activating factor-stimulated eosinophil accumulation in the lung. Fluticasone propionate therefore has increased intrinsic glucocorticoid potency and high topical anti-inflammatory activity.
Johnson
M
M
Respiratory Product Strategy Group, Glaxo Research and Development Limited, Uxbridge, Middlesex, UK.
D000287:Administration, Topical; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D000068298:Fluticasone