Vutikullird Apinya Bee, Gillespie Michael, Song Sharon, Steinfeld Jonathan
1 WCCT Global , Cypress, California.
2 Teva Pharmaceuticals , Frazer, Pennsylvania.
J Aerosol Med Pulm Drug Deliv. 2016 Apr;29(2):207-14. doi: 10.1089/jamp.2015.1226. Epub 2015 Dec 1.
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.
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.
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.
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.
丙酸氟替卡松（Fp）是一种吸入性皮质类固醇，具有公认的安全性和有效性。本研究评估了从一种新型吸入驱动多剂量干粉吸入器（MDPI）吸入的Fp的全身药代动力学，该吸入器不需要吸入与启动的协调配合。
这是一项单中心、开放标签、随机、3期交叉、单剂量研究，纳入年龄在20至45岁（含）的健康日本和白种人受试者。受试者被随机分配到六个治疗序列之一，包括四种吸入Fp MDPI 100μg（总剂量400μg）、Fp MDPI 200μg（总剂量800μg）和Fp Diskus® 100μg（总剂量400μg）的组合。主要目的是评估每种治疗的药代动力学（最大血浆浓度 [Cmax] 和浓度-时间曲线下面积 [AUC]）。还评估了安全性和耐受性。
30名受试者（15名白种人，15名日本人）符合入选标准并被随机分组；所有30名受试者均完成了研究。在评估的吸入Fp总剂量（400和800μg）下，日本和白种人受试者的血浆浓度-时间曲线形状和全身暴露（AUC0-t和Cmax）相似。AUC0-t的几何平均比值（日本/白种人）范围为1.11至1.15，Cmax的几何平均比值范围为0.90至1.05，种族之间无实质性差异。在两个种族组以及合并人群中，Fp MDPI 800μg的全身暴露（AUC0-t和Cmax）最高，其次是Fp MDPI 400μg，最后是Fp Diskus 400μg。没有临床实验室、生命体征或体格检查结果被认为具有临床意义。
对于每个总剂量和吸入器，健康成年日本和白种人受试者吸入单剂量Fp后的全身暴露相当。新型MDPI比Diskus提供了更有效的药物递送，这表明与Diskus相比，Fp MDPI可能在较低的吸入剂量下提供相似的临床疗效。单剂量吸入Fp（400 - 800μg）在健康成年人中通常耐受性良好。
