The Pharmacokinetics of Fluticasone Furoate Given Intranasally in Healthy Subjects Using an Ultra-Sensitive Analytical Assay

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 AUC inf and t 1/2. Median T max was 1.33 h (range=0.75-6.00), mean C max was 13.05±7.59 pg/mL, mean AUC t was 148.48±77.76 pg/mL*h, mean AUC inf was 279.07±187.81 pg/mL*h, and mean t 1/2 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.