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

Br J Clin Pharmacol. 1999 Oct;48(4):579-85. doi: 10.1046/j.1365-2125.1999.00058.x.

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, FEF(25-75) 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adrenal Glands / drug effects
  • Adult
  • Androstadienes / administration & dosage*
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Inflammatory Agents / administration & dosage*
  • Asthma / blood
  • Asthma / drug therapy*
  • Biomarkers / blood
  • Bone and Bones / drug effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Eosinophils / drug effects
  • Female
  • Fluticasone
  • Humans
  • Hydrocortisone / blood
  • Male
  • Osteocalcin / blood
  • Prednisolone / administration & dosage*
  • Time Factors

Substances

  • Androstadienes
  • Anti-Asthmatic Agents
  • Anti-Inflammatory Agents
  • Biomarkers
  • Osteocalcin
  • Prednisolone
  • Fluticasone
  • Hydrocortisone