Exhalation Delivery System Compared to Conventional Nasal Spray

The study looked at the PK of fluticasone propionate given as EDS-FLU, Flonase, and Flovent
The study looked at the PK of fluticasone propionate given as EDS-FLU, Flonase, and Flovent

ATLANTA, GA—EDS-FLU produced higher systemic exposure than Flonase and substantially lower systemic exposure than Flovent 440mcg, indicating that drug deposition is greatly improved with EDS vs. conventional nasal spray, reported John Messina, Jr., PharmD, from OptiNose, Yardley, PA, at the 2017 AAAAI Annual Meeting.

Compared to nasal sprays, the exhalation delivery system (EDS) has shown broader drug delivery in the nasal cavity (particularly superiorly/posteriorly) with less loss to drip-out and swallowing. An improved delivery should lead to greater deposition on respiratory epithelium and thus increase blood levels. Super-sensitive techniques can now detect low picogram levels of fluticasone, which is "trivially absorbed." Dr. Messina Jr. and coauthors from Celerion, Lincoln, NE, conducted a study to assess the pharmacokinetics of fluticasone propionate given as EDS-FLU, Flonase, and Flovent

Part 1 was a 3-way, 3-treatment, 3-sequence randomized cross-over study in 90 healthy subjects that compared systemic exposure of EDS-FLU 186mcg and EDS-FLU 372mcg vs. Flonase 400mcg. Part 2 was a 2-way, 2-treatment, 2-sequence randomized-crossover in 30 mild-moderate asthmatics that compared systemic exposure of FLU-EDS 372mcg and Flovent 440mcg. Secondary objectives of the study included the safety and tolerability of each treatment. Additionally, blood samples from all patients were obtained to determine plasma fluticasone propionate concentrations following administration.

The analysis found EDS-FLU 186mcg produced a higher Cmax vs. Flonase 400mcg (16.0pg/mL vs. 11.7pg/mL; 137.4% geometric mean ratio [GMR]) and similar AUC0-∞ (97.3pg/mL vs. 99.6pg/mL; 97.7% GMR). The EDS-FLU 372mcg dose produced a higher Cmax (23.5pg/mL vs. 11.7pg/mL; 201.5% GMR) and AUC0-∞ (146.6pg/mL vs. 99.6pg/mL; 147.2% GMR) vs. Flonase 400mcg. Additionally, the authors noted that the three different treatments yielded “similar shapes for the concentration-time profiles but different mean values.” Data showed that patients receiving EDS-FLU 372mcg produced the highest mean plasma concentration levels.

In Part 2, EDS-FLU 372mcg resulted in a substantially lower Cmax (25.3pg/mL vs. 40pg/mL; 63.2% GMR) and lower AUC0-∞ than Flovent 440mcg (205.8pg/mL vs. 415.2pg/mL; 49.6% GMR). Additionally, “[plasma] fluticasone propionate concentration values were considerably lower for EDS-FLU 372mcg compared with Flovent HFA 440mcg,” the authors added. No serious adverse events or deaths were reported in either part of the study.

"Similar intranasal doses of EDS-FLU (372mcg) and Flonase (400mcg) are clearly not bioequivalent," Dr. Messina Jr pointed out. Though the difference was small, EDS-FLU exhibited higher systemic exposure than Flonase and lower exposure than Flovent. These findings support greatly improved drug deposition with EDS than with conventional nasal spray, the authors concluded.