Abstract
Purpose It has been previously shown that the complete pharmacokinetic
profile, in particular the elimination phase, of intranasal fluticasone furoate
has not been fully characterized due to the inability to quantify concentrations
at low enough levels. This study was designed to evaluate the pharmacokinetic
profile of intranasal FF using a validated, ultra-sensitive analytical method in
healthy subjects.
Methods This was an open-label, single-dose, two-period, one-treatment,
crossover study. A dose of 880 µg fluticasone furoate was
administered intra nasally. Blood samples for pharmacokinetic analysis were
collected at 23 time points up to 36 h and analyzed for FF plasma levels
using a lower limit of quantitation (LLOQ) of 0.1 pg/mL. Medical
and adverse events (AE) were monitored throughout the study.
Results Eighteen subjects were enrolled in and 17 completed the study.
The results showed that all 17 subjects had measurable fluticasone furoate
plasma concentrations at all time points with a clearly defined elimination
phase, thus allowing estimation of AUCinf and
t1/2. Median Tmax was 1.33 h
(range=0.75–6.00), mean Cmax was
13.05±7.59 pg/mL, mean AUCt was
148.48±77.76 pg/mL*h, mean AUCinf was
279.07±187.81 pg/mL*h, and mean
t1/2 was 31.67±29.23 h. In total 4
subjects (22.2%) experienced 4 AEs.
Conclusion Using a lower LLOQ than what has been previously reported, a
complete characterization of intranasal fluticasone furoate pharmacokinetics,
including a clearly defined terminal elimination phase, was achieved. This
method will allow for further investigations into the pharmacokinetics of
fluticasone furoate.
Key words
bioavailability - pharmacokinetics - pulmonary & respiratory pharmacology - absorption
- bioanalytical method - nasal spray - Fluticasone Furoate