Abstract
Background: 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.Methods: 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 (Cmax) and area under the concentration–time curve from time zero to the last sample with quantifiable concentration (AUCt). For salmeterol, the primary variables for total systemic exposure were Cmax and AUCt and for lung deposition Cmax and AUC up to 30 minutes after study treatment administration (AUC30min).Results: 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 Cmax and AUCt were 0.9901–1.1336 and 0.9448–1.0542, respectively. Ninety percent CIs for salmeterol Cmax, AUC30min, and AUCt ratios were 1.0567–1.2012, 1.0989–1.2255, and 1.0769–1.1829, respectively. Median salmeterol time to maximum concentration (tmax) was 4.0 minutes. Median fluticasone propionate tmax was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9–10 hours for fluticasone propionate.Conclusions: Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.
Highlights
Salmeterol is a potent and selective b2-adrenoceptor agonist that, in addition to the regular management of asthma, is approved in various countries for the maintenance therapy of chronic obstructive pulmonary disease (COPD)
EasyhalerÒ dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease
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 in fasting conditions
Summary
Salmeterol is a potent and selective b2-adrenoceptor agonist that, in addition to the regular management of asthma, is approved in various countries for the maintenance therapy of chronic obstructive pulmonary disease (COPD). EasyhalerÒ dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Methods: 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 lg/inhalation strength) in fasting conditions. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration–time curve (Cmax) and area under the concentration–time curve from time zero to the last sample with quantifiable concentration (AUCt). The primary variables for total systemic exposure were Cmax and AUCt and for lung deposition Cmax and AUC up to 30 minutes after study treatment administration (AUC30min). Conclusions: Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product
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