Pharmacokinetics and Bioavailability of Intranasal Fluticasone in Humans

Abstract

The aim of the studies described in the present report was to determine the systemic bioavailability of intranasal fluticasone propionate (FP) in healthy volunteers and in patients with atopic rhinitis. In addition, the effect that any FP that was absorbed may have on the hypothalamic pituitary (HPA) axis was also determined. In six separate studies, subjects were administered FP intranasally either once or twice daily for up to 7.5 days. In studies where FP was given once daily, doses ranged from 0.2 to 1mg. In studies where FP was given twice daily, dosages up to 2.0mg twice daily were given. At intervals following the last dose of FP, blood samples were taken for determination of plasma levels of FP and, in a number of studies, cortisol. In some studies, urine was collected for 24 hours following the last dose of FP for the determination of urinary cortisol excretion. Following repeated administration of FP (up to 1.0mg twice daily for 7.5 days), plasma levels of FP remained below the lower limit of detection (0.05 μg/L) for the 8-hour investigational period after the last dose of FP. When FP (0.2mg) was administered intranasally to patients with allergic rhinitis after challenge with allergen, plasma levels of FP remained below the lower limit of detection for 6 hours after administration with FP. Following administration of single and repeated doses of FP intranasally (up to 1.0mg twice daily for 7 days), no significant reduction in plasma cortisol concentrations could be measured. In the same subjects dexamethasone (2mg orally) reduced plasma cortisol concentrations from 143.0 ± 6.39 μg/L to < 10 μg/L. Neither single (up to l.Omg) nor repeated (up to 2.0mg twice daily for 7 days) administration of FP caused a significant reduction in urinary cortisol excretion. Even at doses 10 times higher than the dose used clinically, absorption of FP from the nasal mucosa was low (< 2%). It is concluded that any FP that is absorbed from the nasal mucosa is insufficient to exert any measurable effect on the HPA axis.