Bioavailability and disposition of azelastine and fluticasone propionate when delivered by MP29-02, a novel aqueous nasal spray

AIM(S) To determine azelastine hydrochloride (AZE) and fluticasone propionate (FP) bioavailabilities of the novel nasal spray combination product MP 29-02, compared with MP29-02-based products containing only AZE (MP29-02-AZE-mono), FP (MP29-02-FP-mono), marketed AZE and FP single entity products (Astelin (R) and FP Boehringer-Ingelheim; FP-BI). METHODS Two randomized, three period, six sequence, three treatment crossover studies were conducted in healthy subjects. Study 1 administered 200 mu g FP as MP29-02, MP29-02-FP-mono or FP-BI. Study 2 administered 548 mu g AZE as MP29-02, MP29-02-AZE-mono or Astelin (R). Each dose consisted of two sprays/nostril. Serum FP and plasma AZE were followed over 24 (FP) and 120 h (AZE) and quantified by LC-MS/MS. Peak (Cmax) and total exposures AUC(0,tlast) were compared between the treatments by anova. RESULTS Study 1: Average FP Cmax was very low with all products (=10 pg ml-1). FP AUC(0,tlast) point estimates (90% CIs) for MP29-02 : MP29-02-FP-mono and MP29-02 : FP-BI ratios (%) were 93.6 (83.6, 104.7) and 161.1 (137.1, 189.3). Corresponding ratios for Cmax were 91.0 (82.5, 100.4) and 157.4 (132.5, 187.1). Study 2: AZE AUC(0,tlast) point estimates (90% CIs) for MP29-02 : MP29-02-AZE-mono and MP29-02 : Astelin (R) ratios (%) were 98.8 (91.0, 107.4) and 105.5 (95.6, 116.4). Corresponding outcomes for Cmax were 102.7 (92.1, 114.4) and 107.3 (92.6, 124.3). CONCLUSIONS No interactions of AZE and FP were found with the MP29-02 formulation. Azelastine bioavailability was similar for MP29-02 and Astelin (R). Maximum and total FP exposure was higher for MP29-02-based products compared with FP-BI. FP concentrations were generally very low with all investigational products and did not suggest clinically meaningful differences concerning systemic safety.