Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate

TY - JOUR

T1 - Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate

AU - Fardon, Tom C.

AU - Lee, Daniel K. C.

AU - Haggart, Kay

AU - McFarlane, Lesley C.

AU - Lipworth, Brian J.

N1 - dc.publisher: American Thoracic Society dc.description.sponsorship: Supported by a University of Dundee Research Grant.

PY - 2004/11

Y1 - 2004/11

N2 - Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 µg/day) or MF Twisthaler (400, 800, and 1,600 µg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs—as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 µg, 1.85 (1.21–2.82, p = 0.002); FP 1,000 µg, 1.45 (1.07–1.96, p = 0.02); MF 1,600 µg, 1.92 (1.26–2.93, p = 0.001); and MF 800 µg, 1.39 (1.04–1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

AB - Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 µg/day) or MF Twisthaler (400, 800, and 1,600 µg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs—as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 µg, 1.85 (1.21–2.82, p = 0.002); FP 1,000 µg, 1.45 (1.07–1.96, p = 0.02); MF 1,600 µg, 1.92 (1.26–2.93, p = 0.001); and MF 800 µg, 1.39 (1.04–1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

KW - Adrenal suppression

KW - Asthma corticosteroids

KW - Fluticasone

KW - Mometasone

U2 - 10.1164/rccm.200404-500OC

DO - 10.1164/rccm.200404-500OC

M3 - Article

SN - 1073-449X

VL - 170

SP - 960

EP - 966

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 9

ER -