No metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate incubated in a human skin homogenate. The total blood clearance of systemically absorbed fluticasone propionate averages 1,093 mL/min (range, 618 to 1,702 mL/min) after a 1-mg intravenous dose, with renal clearance accounting for less than % of the total. Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5- fluoromethyl carbothioate grouping. This transformation occurs in 1 metabolic step to produce the inactive17-ÃŸ-carboxylic acid metabolite, the only known metabolite detected in man. This metabolite has approximately 2,000 times less affinity 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.
Although patients receiving systemic corticosteroid therapy are more susceptible to secondary infection than patients not receiving corticosteroids, administration via the inhaled route minimizes this risk. Corticosteroid therapy can mask the symptoms of infection and should not be used in cases of bacterial, fungal, or viral infections that are not adequately controlled by anti-infective agents, except in life-threatening circumstances. Fluticasone; salmeterol should be avoided in patients with tuberculosis infections of the respiratory tract if possible. The incidence or course of acute bacterial or viral infection is probably minimally affected by inhaled corticosteroids in immunocompetent individuals; however, close monitoring of patients with immunosuppression is recommended if treatment with an inhaled corticosteroid is necessary.