Dose-response for adrenal suppression with hydrofluoroalkane formulations of fluticasone propionate and beclomethasone dipropionate

S. J. Fowler, L. C. Orr, A. M. Wilson, E. J. Sims, B. J. Lipworth

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Aims: With the recent introduction of hydrofluoroalkane (HFA) inhalers it is important to know the relative systemic safety profiles of inhaled corticosteroids. We therefore decided to compare systemic bioavailability of HFA-beclomethasone dipropionate (BDP) vs HFA-fluticasone propionate (FP). Methods: Sixteen healthy volunteers were randomised in placebo-controlled single blind cross-over fashion to receive 3 weeks with HFA-FP or HFA-BDP, given as 1 week cumulative doubling doses (nominal ex-valve) of 500, 1000 and 2000 μg day-1, with a 1 week placebo run-in and wash-out. Overnight (22.00 h to 08.00 h) and early morning (08.00 h) urinary cortisol/creatinine excretion and 08.00 h serum cortisol were measured after each placebo and dosing period. All data were log-transformed to normalize their distribution. Results: Urine and serum cortisol were suppressed by 2000 μg FP and BDP vs placebo and by 1000 μg BDP vs placebo for urinary cortisol/creatinine (P <0.05). Overnight urinary cortisol/creatinine ratio (the primary endpoint) was suppressed more by 1000 μg BDP vs 1000 μg FP (P <0.05), amounting to a geometric mean fold difference (95% CI) of 1.64 (1.04-2.56). There were also more individual low values less than 3 nmol mmol-1 with BDP than FP at 1000 μg: n = 8/16 vs n = 2/16 (P <0.05). Conclusions: There was dose-related suppression of corrected urinary cortisol/creatinine with the HFA formulations of BDP and FP. Suppression of overnight urinary cortisol/creatinine ratio was significantly greater with HFA-BDP than HFA-FP at 1000 μg. This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP.
    Original languageEnglish
    Pages (from-to)93-95
    Number of pages2
    JournalBritish Journal of Clinical Pharmacology
    Volume52
    Issue number1
    DOIs
    Publication statusPublished - 2001

    Keywords

    • Adrenal suppression
    • Beclomethasone
    • Dipropionate
    • Fluticasone propionate
    • Hydrofluoroalkane inhalers

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