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.

Key words

bioavailability - pharmacokinetics - pulmonary & respiratory pharmacology - absorption - bioanalytical method - nasal spray - Fluticasone Furoate

Publication History

Received: 02 January 2020

Accepted: 29 April 2020

Article published online:
02 June 2020

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