Bioequivalence of fluticasone propionate and salmeterol (FS) given by the FS Spiromax® and Seretide Accuhaler®...

To determine pharmacokinetic (PK) profiles of fluticasone propionate (FP) and salmeterol (SAL) in healthy volunteers following administration as two inhalations from the FS Spiromax 500/50 µg and Seretide Accuhaler 50/500 µg inhalers, without (study 1, n = 79) and with charcoal block (study 2, n = 77). Safety was also assessed.

In two single-center, open-label, randomized two-period crossover studies, PK parameters were calculated from plasma drug concentrations obtained pre-dose through 36 hours post-dose. Bioequivalence was established if the 90% confidence intervals for the geometric mean ratios of the area under the plasma drug concentration-time curve from time zero to the time of the last quantifiable concentration (AUC_0-t) and the maximum observed plasma concentration (C_max) for the comparison of both FP and SAL were within 0.80 - 1.25.

In study 1, in subjects administered FS Spiromax, the mean (standard deviation (SD)) FP AUC_0-t and C_max were 1,622.64 (419.44) pg×h/mL and 151.36 (40.37) pg/mL, respectively, vs. 1,487.52 (341.25) pg×h/mL and 137.57 (33.64) pg/mL with Seretide Accuhaler. Mean (SD) SAL AUC_0-t and C_max with FS Spiromax were 408.42 (155.40) pg×h/mL and 269.48 (105.74) pg/mL, respectively, vs. 401.79 (125.32) pg×h/mL and 265.66 (87.28) pg/mL with Seretide Accuhaler. Comparable data were seen in study 2 with charcoal block. Bioequivalence of FS Spiromax with Seretide Accuhaler was observed both without and with charcoal block for FP and SAL for both AUC_0-t and C_max. Both study treatments were well tolerated, with a similar incidence of adverse events reported with the single use of FS Spiromax (23% study 1, 16% study 2) and Seretide Accuhaler (22%, 15%).

FS Spiromax 500/50 µg (± charcoal block) was bioequivalent to Seretide Accuhaler 50/500µg.
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