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

Aims To determine the systemic dose-response relationships with oral predni solone and inhaled fluticasone propionate administered in a putative 11 : 1 mg equivalent basis, in terms of effects on adrenal, bone and haematologic al markers. Methods Twelve asthmatic patients mean (s.e.) age, 28.8 [3.3] years, FEV1 9 4.7 [3.6]% predicted, FEF25-75 65.5 [6.1]% predicted were studied in a doub le-blind, double dummy randomised crossover design comparing placebo, inhal ed fluticasone propionate via volumatic spacer given twice a day (ex actuat or dose 0.44 mg day(-1), 0.88 mg day(-) (1), 1.76 mg day(-1)) and oral pred nisolone 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 cros sover. Measurements were made at 08.00 h after the last dose of each dose l evel 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 cor tisol being greater than osteocalcin or eosinophils. For cortisol suppressi on we observed an 8.5:1 mg relative potency ratio comparing prednisolone wi th fluticasone propionate. Patients taking high dose inhaled fluticasone pr opionate should therefore be screened for evidence of impaired adrenal rese rve.