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

OBJECTIVE To evaluate the dose-response relationship for adrenocortical act ivity with fluticasone propionate (FP) and to assess basal and dynamic mark ers 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 m id expiratory flow rate (FEF25-75): 58.1% predicted. A single blind study d esign 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 dail y divided dosing at 0800 h and 2200 h at doses of 375 mu g, 875 mu g, and 1 750 mu g per day. MEASUREMENTS A 100 mu g iv bolus hCRF test was performed at 0800h after the run-in and washout periods. Blood samples were taken for 0800h serum corti sol and osteocalcin as well as an overnight 10 h urine collection for corti sol/creatinine excretion after the run-in period, each dose of active treat ment and washout. RESULTS For serum cortisol (pre and post hCRF stimulation) there was no sig nificant 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) a nd post hCRF were runin: 690.9 (42.9), washout: 719.1 (43.8). There was a s ignificant (P < 0.05) difference between run-in vs medium and high doses fo r 0800h serum cortisol, overnight urinary cortisol and overnight urinary co rtisol/creatinine excretion; and vs high dose for serum osteocalcin. The fo ld 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 urin ary cortisol/creatininne 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 suppressio n with treatment. The suppressive effects of fluticasone propionate on adre nocortical activity were greater than those observed on osteocalcin.