Dose-response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics

Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1274-7. doi: 10.1164/ajrccm.156.4.97-03029.

Abstract

A single blind randomized crossover trial was performed comparing placebo (PL); low (L), medium (M) and high (H) doses of fluticasone propionate (FP) L: 330 microg, M: 770 microg, H: 1,540 microg per day and triamcinolone acetonide (TAA) L: 400 microg, M: 800 microg, H: 1,600 microg per day. Each drug was given twice daily over a total of 9 d, with 3 d for each dose level. Each 9-d drug sequence was preceded by a 3-d placebo, and was separated by a 12-d washout period. Twelve mild-to-moderate, stable adult asthmatics, mean (SEM) age, 34.3 (2.9) yr, mean FEV1: 82.1 (2.0) % predicted, and FEF25-75%: 53.6 (5.5) % predicted, receiving up to 400 microg of inhaled corticosteroid per day, were studied. After each 3-d treatment period, blood samples were taken for 8:00 A.M. serum cortisol. Ten-hour overnight urine collections were taken for measurement of urinary cortisol and corrected for creatinine excretion, starting at 10:00 P.M. following the sixth dose. For 8:00 A.M. serum cortisol compared with PL there was significant (p < 0.001) dose-related suppression with FP but not with TAA, which amounted to a 2.03-fold ratio for H FP versus H TAA. For corrected urinary cortisol/creatinine excretion, there was a significant (p < 0.005) dose-related suppression for FP but not for TAA. This amounted to a 1.9-fold ratio for H FP versus H TAA. For doses < 1,000 microg/d, the number of individual results with an abnormal low urinary cortisol value (< 10 nmol/10 h) were: 10/24 for FP versus 3/24 for TAA (p < 0.005). In conclusion, for 8:00 A.M. serum cortisol and overnight corrected urinary cortisol/creatinine excretion, there was significant dose-related suppression with FP but not with TAA. For both of these parameters at the highest dose of both drugs, this amounted to a two-fold ratio in suppression.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Administration, Topical
  • Adult
  • Androstadienes / administration & dosage*
  • Androstadienes / therapeutic use
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / physiopathology
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluticasone
  • Forced Expiratory Flow Rates
  • Humans
  • Hydrocortisone / antagonists & inhibitors*
  • Hydrocortisone / blood
  • Hydrocortisone / urine
  • Male
  • Predictive Value of Tests
  • Regression Analysis
  • Single-Blind Method
  • Triamcinolone Acetonide / administration & dosage*
  • Triamcinolone Acetonide / therapeutic use

Substances

  • Androstadienes
  • Anti-Inflammatory Agents
  • Fluticasone
  • Triamcinolone Acetonide
  • Hydrocortisone