The Pharmacokinetics of Fluticasone Furoate Given Intranasally in Healthy Subjects Using an Ultra-Sensitive Analytical AssayFunding: This study was sponsored and funded by Pharma Medica Research Inc.
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 wordsbioavailability - pharmacokinetics - pulmonary & respiratory pharmacology - absorption - bioanalytical method - nasal spray - Fluticasone Furoate
Received: 02 January 2020
Accepted: 29 April 2020
02 June 2020 (online)
© Georg Thieme Verlag KG
Stuttgart · New York
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