Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

Abstract

Aims: To measure and compare the systemic bioavailability of fluticasone propionate aqueous nasal spray and a new nasal drop formulation, using a sensitive analytical method and high dose regimen.

Methods: Volunteers received four 800 microg doses of fluticasone propionate as a nasal spray or drops over 2 days, separated by an 8 h dose interval. On day 2, blood samples were collected for assay of fluticasone propionate plasma concentrations.

Results: The mean systemic exposure, for both formulations was 8.5 pg x ml(-1) x h (drops) and 67.5 pg x ml(-1) x h (spray). Mean absolute bioavailabilities were estimated to be 0.06% (drops) and 0.51% (spray), by reference to historical intravenous data.

Conclusions: Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.

Figure 1

Individual plasma concentrations of fluticasone propionate in 12 healthy subjects under approximate steady-state conditions during an 8 h dosing interval following (a) 800 µg tds fluticasone propionate aqueous nasal spray or (b) 800 µg tds fluticasone propionate nasal drops. (c) Plasma AUC and absolute bioavailability (F) of intranasal fluticasone propionate relative to intravenous administration and in comparison with oral inhalation (normalized to 800 µg doses, n = 12).