Clinical Information

Inhaled corticosteroids are the single most effective therapy for adult patients with asthma. Even low doses of inhaled corticosteroids have been shown to reduce mortality related to asthma. The September 2007 issue of Pediatrics reported that "Verification of (asthma) treatment adherence by objective measures remains necessary."(1) In this pediatric asthma adherence study, the 104 children with asthma and their parents grossly overestimated their medication adherence. Over 1 of 3 responses reported full compliance to medications when no medications had been taken. Over 46% of individuals exaggerated their adherence by at least 25%. The authors concluded that "Under the best of conditions in this study, accuracy of self-report was insufficient to provide a stand-alone measure of adherence."(1,2)

Fluticasone propionate (FP) is an inhaled corticosteroid with antiinflammatory and immunosuppressive properties commonly used for the treatment of asthma, airway inflammation, and allergic rhinitis. FP is typically well tolerated and has a low risk for adverse systemic effects when utilized at recommended therapeutic doses. However, noncompliance with recommended FP therapy may result in poorly controlled asthma or misinterpretation of the patient's therapeutic responsiveness. Patients with excessive exposure to FP may present with clinical features of Cushing syndrome but with evidence of hypothalamus-pituitary-adrenal axis suppression, including suppressed cortisol levels. Conversely, a patient not administering the drug as recommended may have their therapeutic responsiveness interpreted, in error by the patient or clinician, as steroid resistance.

FP has low oral bioavailability and high hepatic first-pass metabolism, which results in low plasma FP concentrations; any systemic levels are believed to occur through adsorption from the lungs. Native FP absorbed by the gastrointestinal tract (<1% total FP) is rapidly metabolized by cytochrome P450 isoform 3A4 to yield fluticasone 17-beta-carboxylic acid, its primary metabolic product.(3) Fluticasone 17-beta-carboxylic acid is pharmacologically inactive and has increased water solubility such that it is excreted in urine. Accordingly, fluticasone 17-beta-carboxylic acid is detected in urine in individuals recently exposed to inhaled FP therapy. Fluticasone 17-beta-carboxylic acid may be detected in urine as early as 16 to 24 hours following a patient's first administration of low-dose (220 mcg) FP therapy. The window of detection for fluticasone 17-beta-carboxylic acid is 6 days following cessation of FP therapy.