FLIXONASE Nasal drops Ref.[27691] Active ingredients: Fluticasone

Absorption

After recommended doses of intranasal fluticasone propionate plasma levels are low. Systemic bioavailability for the nasal drop formula is extremely low (mean value 0.06%).

Following intravenous administration the pharmacokinetics of fluticasone propionate are proportional to the dose, and can be described by three exponentials.

Absolute oral bio-availability is negligible (<1%) due to a combination of incomplete absorption from the gastro-intestinal tract and extensive first pass metabolism.

Distribution

Fluticasone propionate is extensively distributed within the body (Vss is approximately 300 litre). Plasma protein binding is 91%.

Biotransformation/Elimination

After intravenous administration, fluticasone propionate has a very high clearance (estimated Cl 1.1 litre/min) indicating extensive hepatic extraction. It is extensively metabolised by CYP3A4 enzyme to an inactive carboxylic derivative.

Peak plasma concentrations are reduced by approximately 98% within 3-4 hours, and only low plasma concentrations are associated with the terminal half life, which is approximately 8 hours.

Following oral administration of fluticasone propionate, 87-100% of the dose is excreted in the faeces as parent compound or as metabolites.

At doses in excess of those recommended for therapeutic use, only class effects typical of potent corticosteroids have been shown in repeat dose toxicity tests, reproductive toxicology and teratology studies. Fluticasone propionate has no mutagenic effect in vitro or in vivo, no tumorigenic potential in rodents and is non-irritant and non-sensitising in animals.