Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1      Pharmacodynamic properties

Fluticasone propionate given by inhalation at recommended doses has a potent glucocorticoid anti-inflammatory action within the lungs, which results in reduced symptoms and exacerbations of asthma.
Fluticasone propionate containing medications in asthma during pregnancy

An observational retrospective epidemiological cohort study utilising electronic health records from the United Kingdom was conducted to evaluate the risk of major congenital malformations following first trimester exposure to inhaled fluticasone propionate alone and salmeterol-fluticasone propionate combination relative to non-fluticasone propionate containing inhaled corticosteroids. No placebo comparator was included in this study.

Within the asthma cohort of 5362 first trimester inhaled corticosteroids- exposed pregnancies, 131 diagnosed major congenital malformations were identified; 1612 (30%) were exposed to fluticasone propionate or salmeterol- fluticasone propionate of which 42 diagnosed major congenital malformations were identified. The adjusted odds ratio for major congenital malformations diagnosed by 1 year was 1.1 (95%CI: 0.5 – 2.3) for fluticasone propionate exposed vs non-fluticasone propionate inhaled corticosteroids exposed women with moderate asthma and 1.2 (95%CI: 0.7 – 2.0) for women with considerable to severe asthma. No difference in the risk of major congenital malformations was identified following first trimester exposure to fluticasone propionate alone versus salmeterol-fluticasone propionate combination.
Absolute risks of major congenital malformations across the asthma severity strata ranged from 2.0 to 2.9 per 100 fluticasone propionate-exposed pregnancies which is comparable to results from a study of 15,840 pregnancies unexposed to asthma therapies in the General Practice Research Database (2.8 major congenital malformations events per 100 pregnancies).

Pharmacokinetic Properties

5.2      Pharmacokinetic properties
Following inhaled dosing, systemic availability of the nebulised fluticasone propionate in healthy volunteers is estimated at 8% as compared with up to          26% received from the metered dose inhaler presentation. Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged. The remainder of the dose may be swallowed.
Absolute oral bioavailability is negligible (<1%) due to a combination of incomplete absorption from the GI tract and extensive first-pass metabolism.
87-100% of an oral dose is excreted in the faeces, up to 75% as parent compound. There is also a non-active major metabolite.

After an intravenous dose, fluticasone propionate is extensively distributed in the body. The very high clearance rate indicates extensive hepatic clearance.