Dose response with fluticasone propionate on adrenocortical activity and recovery of basal and stimulated responses after stopping treatment

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Abstract
OBJECTIVE To evaluate the dose–response relationship for adrenocortical activity with fluticasone propionate (FP) and to assess basal and dynamic markers after stopping treatment for 3 days. PATIENTS AND DESIGN Fourteen asthmatic patients were recruited: mean age 33.3 years, forced expiratory volume in 1 s (FEV1): 91.3% predicted, forced mid expiratory flow rate (FEF25–75): 58.1% predicted. A single blind study design was used comparing a placebo run‐in with sequentially low, medium and high doses of FP and a placebo washout. All active treatments, placebo and washout were each for 3 days. FP was given at steady‐state with twice daily divided dosing at 0800 h and 2200 h at doses of 375 μg, 875 μg, and 1750 μg per day. MEASUREMENTS A 100 μg iv bolus hCRF test was performed at 0800h after the run‐in and washout periods. Blood samples were taken for 0800h serum cortisol and osteocalcin as well as an overnight 10 h urine collection for cortisol/creatinine excretion after the run‐in period, each dose of active treatment and washout. RESULTS For serum cortisol (pre and post hCRF stimulation) there was no significant difference between placebo and washout values. Mean (SE) cortisol (nmol/1) values pre hCRF were run‐in: 644.5 (59.7), washout: 550.3 (42.8) and post hCRF were run‐in: 690.9 (42.9), washout: 719.1 (43.8). There was a significant (P < 0.05) difference between run‐in vs medium and high doses for 0800 h serum cortisol, overnight urinary cortisol and overnight urinary cortisol/creatinine excretion; and vs high dose for serum osteocalcin. The fold difference (95% CI for difference) between run‐in and high dose was: 2.2 (1.5–3.2) for overnight urinary cortisol, 2.5 (1.5–4.1) for overnight urinary cortisol/creatinine, 2.0 (1.1–3.6) for serum cortisol, and 1.2 (1.1–1.3) for serum osteocalcin. CONCLUSION Fluticasone propionate exhibited dose related adrenal suppression with treatment. The suppressive effects of fluticasone propionate on adrenocortical activity were greater than those observed on osteocalcin.