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 micrograms, 875 micrograms, and 1750 micrograms per day.
Measurements: A 100 micrograms i.v. bolus hCRF test was performed at 0800 h after the run-in and washout periods. Blood samples were taken for 0800 h 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.