Pharmacokinetic Comparison of a Unit Dose Dry Powder Inhaler with a Multidose Dry Powder Inhaler for Delivery of Fluticasone Furoate

摘要

Background: The unit dose dry powder inhaler (UD-DPI) is being considered as an alternative inhaler platform that, if developed, has the potential to improve access to inhaled respiratory medicines in developing countries. Aim: This study compared the systemic exposure of fluticasone furoate after delivery from the UD-DPI with that from the ELLIPTA ? inhaler. Methods: This open-label, five-way cross-over, randomized, single-dose study in healthy subjects evaluated fluticasone furoate systemic exposure of three dose strengths (using four inhalations), 4?×?80?μg [320?μg], 4?×?100?μg [400?μg], and 4?×?140?μg [560?μg]), and two percentages of drug in lactose blends (0.6% and 0.8% by weight) after delivery from the UD-DPI compared with systemic exposures from the ELLIPTA inhaler (4?×?100?μg [400?μg] dose, 0.8% lactose blend). The primary treatment comparisons were area under the concentration–time curve from time 0 to 6 hours [AUC 0–6 ] and maximum plasma concentration [ C max ]. Results: After single-dose administration of fluticasone furoate, systemic exposure was lower from all UD-DPI formulations versus the ELLIPTA inhaler in terms of both AUC 0–6 [AUC 0–6 geometric least squares mean (GLM) ratios confidence interval (90% CI) for: UD-DPI (400?μg 0.8% blend)/ELLIPTA: 0.61 (0.55–0.67) and C max GLM (90% CI) for: UD-DPI (400?μg 0.8% blend)/ELLIPTA: 0.56 (0.49–0.64)]. Systemic exposures were ～10% lower for fluticasone furoate UD-DPI for the 0.8% blend versus the 0.6% blend [GLM ratio (90% CI); 0.90 (0.81–1.00) for AUC 0–6 and 0.89 (0.77–1.01) for C max ], and increasing doses of fluticasone furoate from the UD-DPI showed systemic exposures that were approximately dose proportional. All treatments were well tolerated. Conclusions: Fluticasone furoate systemic exposure was lower from the UD-DPI than from the ELLIPTA inhaler, but the UD-DPI formulations did demonstrate detectable systemic levels and approximate dose proportionality. Together with the good tolerability shown, these data support further evaluation of the UD-DPI as a potential device for delivering inhaled respiratory drugs.