Dose-response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics.
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.
Wilson
A M
AM
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
McFarlane
L C
LC
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000287:Administration, Topical; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone; D005540:Forced Expiratory Flow Rates; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors* / Q000097:blood / Q000652:urine; D008297:Male; D011237:Predictive Value of Tests; D012044:Regression Analysis; D016037:Single-Blind Method; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000627:therapeutic use
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000068298:Fluticasone; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone