Pharmacokinetics of Salmeterol and Fluticasone Propionate Delivered in Combination via Easyhaler and Diskus Dry Powder Inhalers in Healthy Subjects.

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 (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).

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 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.

CONCLUSIONS

Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.