Orion Pharma, Orion Corporation, Espoo, Finland .
J Aerosol Med Pulm Drug Deliv. 2018 Oct;31(5):290-297. doi: 10.1089/jamp.2017.1437. Epub 2018 Mar 1.
Easyhaler dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide Diskus DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference.
Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 μg/inhalation strength) in fasting conditions. Blood samples were drawn before dosing and at frequent time points between 2 minutes and 34 hours after dosing for determination of drug concentrations. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration-time curve (C) and area under the concentration-time curve from time zero to the last sample with quantifiable concentration (AUC). For salmeterol, the primary variables for total systemic exposure were C and AUC and for lung deposition C and AUC up to 30 minutes after study treatment administration (AUC).
One of the Easyhaler test products met all the criteria for bioequivalence with the reference. The 96.7% confidence intervals (CIs) for the test/reference ratios of fluticasone propionate C and AUC were 0.9901-1.1336 and 0.9448-1.0542, respectively. Ninety percent CIs for salmeterol C, AUC, and AUC ratios were 1.0567-1.2012, 1.0989-1.2255, and 1.0769-1.1829, respectively. Median salmeterol time to maximum concentration (t) was 4.0 minutes. Median fluticasone propionate t was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9-10 hours for fluticasone propionate.
Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.
含有沙美特罗和丙酸氟替卡松的 Easyhaler 干粉吸入器（DPI）被开发用于治疗哮喘和慢性阻塞性肺疾病。对三种不同的沙美特罗/丙酸氟替卡松 Easyhaler 试验品（芬兰 Orion Pharma）与参比产品 Seretide Diskus DPI（英国 GlaxoSmithKline）进行了比较，以研究任何试验品是否与参比产品具有生物等效性。
在一个中心进行了一项开放、随机的四周期交叉药理学研究，共纳入 65 名健康志愿者，空腹条件下单次给予（50/500μg/吸强度，各吸两喷）后，比较沙美特罗和丙酸氟替卡松的肺部沉积和全身总暴露。在给药前和给药后 2 分钟至 34 小时之间频繁采集血样，以测定药物浓度。丙酸氟替卡松的全身总暴露和肺部沉积的主要变量为浓度-时间曲线的最大浓度（C）和从零时到最后一个可定量浓度的浓度-时间曲线下面积（AUC）。对于沙美特罗，全身总暴露的主要变量为 C 和 AUC，肺部沉积的主要变量为 C 和 AUC，在研究治疗后 30 分钟内（AUC）。
其中一种 Easyhaler 试验品完全符合参比品的生物等效性标准。丙酸氟替卡松 C 和 AUC 的试验/参比比值的 96.7%置信区间（CI）分别为 0.9901-1.1336 和 0.9448-1.0542。沙美特罗 C、AUC 和 AUC 比值的 90%CI 分别为 1.0567-1.2012、1.0989-1.2255 和 1.0769-1.1829。沙美特罗 C 的中位数达峰时间（t）为 4.0 分钟。丙酸氟替卡松 t 从 1.5 至 2.0 小时不等。沙美特罗的终末消除半衰期为 11 小时，丙酸氟替卡松的半衰期为 9-10 小时。
沙美特罗/丙酸氟替卡松 Easyhaler 与参比产品具有生物等效性。
