Advair Diskus Clinical Pharmacology

Drug Library
Advair Diskus - Clinical Pharmacology [Salmeterol/Fluticasone]

Metabolism:

The total clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total. The only circulating metabolite detected in man is the 17 -carboxylic acid derivative of fluticasone propionate, which is formed through the cytochrome P450 3A4 pathway. This metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

Elimination:

Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.

Special Populations:

Hepatic Impairment:

Since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored.

Gender:

Full pharmacokinetic profiles were obtained from 9 female and 16 male patients with asthma given fluticasone propionate inhalation powder 500 mcg twice daily using the DISKUS device and from 14 female and 43 male patients with COPD given 250 or 500 mcg twice daily. No overall differences in fluticasone propionate pharmacokinetics were observed.

Age:

No relationship between fluticasone propionate systemic exposure and age was observed in 57 patients with COPD (aged 40 to 82 years) given 250 or 500 mcg twice daily.

Other:

Formal pharmacokinetic studies using fluticasone propionate have not been conducted in other special populations.