FLUTICASONE PROPIONATE Cream Ref.[6857] Active ingredients: Fluticasone

Pharmacokinetic data for the rat and the dog indicate rapid elimination and extensive metabolic clearance. Bioavailability is very low after topical or oral administration, due to limited absorption through the skin or from the gastrointestinal tract, and because of extensive first-pass metabolism. Distribution studies have shown that only minute traces of orally administered compound reach the systemic circulation, and that any systemically available radiolabel is rapidly eliminated in the bile and excreted in the faeces.

Fluticasone propionate does not persist in any tissue, and does not bind to melanin. The major route of metabolism is hydrolysis of the S-fluoromethyl carbothioate group, to yield a carboxylic acid (GR36264), which has very weak glucocorticoid or anti-inflammatory activity. In all test animal species, the route of excretion of radioactivity is independent of the route of administration of radiolabelled fluticasone propionate.

Excretion is predominantly faecal and is essentially complete within 48 hours. In man, too, metabolic clearance is extensive, and elimination is consequently rapid.

Thus, drug entering the system circulation via the skin will be rapidly inactivated. Oral bioavailability approaches zero, due to poor absorption and extensive first-pass metabolism. Therefore, systemic exposure to any ingestion of the topical formulation will be low.

Non-clinical studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, fertility and general reproductive performance revealed no special hazard for humans, other than that anticipated for a potent steroid.

Reproductive studies suggest that subcutaneous administration of fluticasone propionate to pregnant animals at doses much higher that the human topical dose can result in abnormalities of foetal development including cleft palate/lip.