Mometasone furoate has minimal effects on the hypothalamic-pituitary-adrenal axis when delivered at high doses

Study objectives: To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI). Design: Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies. Patients: Adults with mild-to-moderate persistent asthma. Interventions: Study 1 (12 patients per treatment group; MF DPI at 200 mug bid, 400 mug qd, 800 mug qd, or 1,200 mug qd). Study 2 (16 patients per treatment group; MF DPI at 400 mug bid or 800 mug bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 mug bid or 800 mug bid, or fluticasone propionate [FP] at 880 mug bid by MDI). Measurements and results: Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-mug qd dosage and approximately 250 pg/mL at the 1,200-mug qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 mug bid, and 181.0 +/- 10.9 pg/mL for 800 mug bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 mug bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 mug bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 mug bid, MF DPI 800 mug bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 mug bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 mug bid was similar to placebo treatment at all time points. Conclusions: The MF 800-mug bid dosage (1,600 mug/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.