| Indication |
For the maintenance treatment of asthma as prophylactic therapy
and for patients requiring oral corticosteroid therapy for asthma. |
| Pharmacodynamics |
Fluticasone propionate, a medium-potency synthetic
corticosteroid, is used topically to relieve inflammatory and pruritic
symptoms of dermatoses and psoriasis, intranasally to manage symptoms of
allergic and non-allergic rhinitis, and orally for the treatment of
asthma. |
| Mechanism of action |
Binds to the glucocorticoid receptor. Unbound corticosteroids
cross the membranes of cells such as mast cells and eosinophils, binding
with high affinity to glucocorticoid receptors (GR). The results
include alteration of transcription and protein synthesis, a decreased
release of leukocytic acid hydrolases, reduction in fibroblast
proliferation, prevention of macrophage accumulation at inflamed sites,
reduction of collagen deposition, interference with leukocyte adhesion
to the capillary wall, reduction of capillary membrane permeability and
subsequent edema, reduction of complement components, inhibition of
histamine and kinin release, and interference with the formation of scar
tissue. In the management of asthma, the glucocorticoid receptor
complexes down-regulates proinflammatory mediators such as
interleukin-(IL)-1, 3, and 5, and up-regulates anti-inflammatory
mediators such as IkappaB [inhibitory molecule for nuclear factor
kappaB1], IL-10, and IL-12. The antiinflammatory actions of
corticosteroids are also thought to involve inhibition of cytosolic
phospholipase A2 (through activation of lipocortin-1 (annexin)) which
controls the biosynthesis of potent mediators of inflammation such as
prostaglandins and leukotrienes. |
| Absorption |
The extent of percutaneous absorption of topical corticosteroids
is determined by many factors, including the vehicle and the integrity
of the epidermal barrier. |
| Volume of distribution |
|
| Protein binding |
91% |
| Metabolism |
Fluticasone propionate is metabolized in the liver by cytochrome
P450 3A4-mediated hydrolysis of the 5-fluoromethyl carbothioate
grouping. This transformation occurs in 1 metabolic step to produce the
inactive 17-(beta)-carboxylic acid metabolite, the only known metabolite
detected in man. |
| Route of elimination |
Not Available |
| Half life |
10 hours |
| Clearance |
|
| Toxicity |
Not Available |
