Flixotide Mechanism of Action





Agencia Lei Va Hong
Full Prescribing Info
Pharmacology: Pharmacodynamics: FLIXOTIDE given by inhalation at recommended doses has potent glucocorticoid activity in the airway. The potent anti-inflammatory action improves the symptomatic control of asthma, allows reduction of other drugs, such as rescue bronchodilators, and may limit the risk of decline in lung function over time. The low systemic bioavailability of FLIXOTIDE provides a better risk: benefit outcome without the adverse effects that accompany systemically administered corticosteroids.
Pharmacokinetics: Following inhaled doses of 2000mcg per day (1000mcg twice daily) for 14 days in healthy volunteers, peak plasma concentrations of about 0.3ng/mL were observed at 30-60 minutes post-dosing.
Absorption: The absolute bioavailability of fluticasone propionate for each of the available inhaler devices has been estimated from within and between study comparisons of inhaled and intravenous pharmacokinetic data based on AUC(0-infinity) data. In healthy adult subjects the absolute bioavailability has been estimated for FLIXOTIDE Inhaler (10.9%). Since the bioavailability of the swallowed portion of an inhaled dose which reaches the gastrointestinal tract is virtually zero, the systemic absorption would be a reflection of the amount of drug reaching the lungs.
FLIXOTIDE has many pharmacokinetic and pharmacodynamic features similar to those of other inhaled glucocorticoids used for the treatment of asthma. However, in contrast to these other steroids, a combination of incomplete gastrointestinal absorption and high first pass metabolic extraction ensures that virtually no FLIXOTIDE swallowed after oral inhalation reaches the systemic circulation.
Metabolism: In animals and humans, propellant HFA-134a was eliminated rapidly in the breath, with no evidence of metabolism or accumulation in the body. Time to maximum plasma concentration (tmax) and mean residence time are both extremely short, leading to a transient appearance of HFA-134a in the blood with no evidence of accumulation.
Distribution: Following intravenous administration, the pharmacokinetics of FLIXOTIDE are proportional to the dose. FLIXOTIDE is extensively distributed within the body. The volume of distribution at steady state is approximately 300 litres and has a very high clearance which is estimated to be 1.1 litre/minute indicating extensive hepatic extraction. Peak plasma fluticasone propionate 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.
Excretion: Studies with radiolabelled and unlabelled FLIXOTIDE administered orally to human volunteers indicate that the majority of the dose (87%-100%) is excreted in the faeces, with up to 75% as unchanged drug, depending on the dose administered. Between 1% and 5% of the dose is excreted as metabolites in urine.
Single oral doses of 16mg in healthy volunteers produced plasma levels of less than 0.5ng/mL.
Single intravenous doses of 2mg in healthy volunteers revealed that the clearance of FLIXOTIDE approximates liver blood flow (900ml/min), with renal clearance (0.11mL/min) accounting for less than 1%. These results indicate that hepatic extraction is almost complete and that oral bioavailability is close to zero.
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