Short‐term dose‐response relationships for the relative systemic effects of oral prednisolone and inhaled fluticasone in asthmatic adults

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Abstract
Aims To determine the systemic dose–response relationships with oral prednisolone and inhaled fluticasone propionate administered in a putative 11:1 mg equivalent basis, in terms of effects on adrenal, bone and haematological markers. Methods Twelve asthmatic patients mean (s.e.) age, 28.8 [3.3] years, FEV1 94.7 [3.6]% predicted, FEF25–75 65.5 [6.1]% predicted were studied in a double-blind, double dummy randomised crossover design comparing placebo, inhaled fluticasone propionate via volumatic spacer given twice a day (ex actuator dose 0.44 mg day−1, 0.88 mg day−1, 1.76 mg day−1 ) and oral prednisolone given once daily (5 mg day−1, 10 mg day−1, 20 mg day−1 ). All treatments were for 4 days at each dose level with a 7-day washout at crossover. Measurements were made at 08.00 h after the last dose of each dose level for plasma cortisol, serum osteocalcin and blood eosinophil count. Results There were significant dose-related effects for suppression of all three endpoints with both prednisolone and fluticasone propionate. Parallel slope analysis revealed a calculated dose ratio for relative potency of 8.5:1 mg (95% CI 5.7–11.2) comparing Pred with FP for morning cortisol. The magnitude of suppression with FP was less for osteocalcin and eosinophils than for cortisol. Conclusions Systemic tissues exhibit different dose–response relationships for the effects of inhaled and oral corticosteroids with suppression of cortisol being greater than osteocalcin or eosinophils. For cortisol suppression we observed an 8.5:1 mg relative potency ratio comparing prednisolone with fluticasone propionate. Patients taking high dose inhaled fluticasone propionate should therefore be screened for evidence of impaired adrenal reserve.