Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic Group: Nasal preparations, Corticosteroids
ATC code: R01AD08

Fluticasone propionate has potent anti-inflammatory activity when used topically on the nasal mucosa.
Fluticasone propionate causes little or no HPA axis suppression following intranasal administration.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

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.