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

Tom C. Fardon, Daniel K. C. Lee, Kay Haggart, Lesley C. McFarlane, Brian J. Lipworth

    Research output: Contribution to journalArticle

    80 Citations (Scopus)

    Abstract

    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.
    Original languageEnglish
    Pages (from-to)960-966
    Number of pages7
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume170
    Issue number9
    DOIs
    Publication statusPublished - Nov 2004

    Fingerprint

    Mometasone Furoate
    Powders
    Hydrocortisone
    Creatinine
    Biological Availability
    Osteocalcin
    fluticasone furoate
    Fluticasone

    Keywords

    • Adrenal suppression
    • Asthma corticosteroids
    • Fluticasone
    • Mometasone

    Cite this

    Fardon, Tom C. ; Lee, Daniel K. C. ; Haggart, Kay ; McFarlane, Lesley C. ; Lipworth, Brian J. / Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate. In: American Journal of Respiratory and Critical Care Medicine. 2004 ; Vol. 170, No. 9. pp. 960-966.
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    abstract = "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.",
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    Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate. / Fardon, Tom C.; Lee, Daniel K. C.; Haggart, Kay; McFarlane, Lesley C.; Lipworth, Brian J.

    In: American Journal of Respiratory and Critical Care Medicine, Vol. 170, No. 9, 11.2004, p. 960-966.

    Research output: Contribution to journalArticle

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    AU - Fardon, Tom C.

    AU - Lee, Daniel K. C.

    AU - Haggart, Kay

    AU - McFarlane, Lesley C.

    AU - Lipworth, Brian J.

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    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.

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