Pharmacokinetics, Safety, and Tolerability of a New Fluticasone Propionate Multidose Dry Powder Inhaler Compared With Fluticasone Propionate Diskus(®) in Healthy Adults.

BACKGROUND

Fluticasone propionate (Fp) is an inhaled corticosteroid with well-established safety and efficacy profiles. This study evaluated the systemic pharmacokinetics of Fp inhaled from a novel, inhalation-driven multidose dry powder inhaler (MDPI) that does not require coordination of actuation with inhalation.

METHODS

This was a single-center, open-label, randomized, 3-period crossover, single-dose study in healthy Japanese and Caucasian subjects aged 20-45 years, inclusive. Subjects were randomized to one of six treatment sequences including combinations of four inhalations of Fp MDPI 100 μg (400 μg total dose), Fp MDPI 200 μg (800 μg total dose), and Fp Diskus(®) 100 μg (400 μg total dose). The primary objective was to assess pharmacokinetics (maximum plasma concentration [Cmax] and area under concentration-vs.-time curve [AUC]) for each treatment. Safety and tolerability were also assessed.

RESULTS

Thirty subjects (15 Caucasian, 15 Japanese) met entry criteria and were randomized; all 30 subjects completed the study. At the inhaled Fp total doses evaluated (400 and 800 μg), the shapes of plasma concentration-vs.-time curves and systemic exposure (AUC0-t and Cmax) were similar in Japanese and Caucasian subjects. Geometric mean ratios (Japanese/Caucasian) for AUC0-t ranged from 1.11 to 1.15, and for Cmax ranged from 0.90 to 1.05, with no substantial differences between ethnic groups. In both ethnic groups, and in the combined population, systemic exposure (AUC0-t and Cmax) was highest for Fp MDPI 800 μg, followed by Fp MDPI 400 μg, and last by Fp Diskus 400 μg. No clinical laboratory, vital signs, or physical examination findings were considered clinically significant.

CONCLUSIONS

Systemic exposure following inhaled single doses of Fp was comparable in healthy adult Japanese and Caucasian subjects for each total dose and inhaler. The new MDPI provided more efficient drug delivery than Diskus, suggesting that Fp MDPI may provide similar clinical efficacy at a lower inhaled dose compared with Diskus. Single-dose inhaled Fp (400-800 μg) was generally well tolerated in healthy adults.