Am. J. Respir. Crit. Care Med., Volume 156, Number 4, October 1997, 1274-1277

Dose-response Effect for Adrenal Suppression with Repeated Twice Daily Inhaled Fluticasone Propionate and Triamcinolone Acetonide in Adult Asthmatics

ANDREW M. WILSON, LESLEY C. MCFARLANE, and BRIAN J. LIPWORTH

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland

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 µg, M: 770 µg, H: 1,540 µg per day and triamcinolone acetonide (TAA) L: 400 µg, M: 800 µg, H: 1,600 µg 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 FEF_25-75%: 53.6 (5.5) % predicted, receiving up to 400 µg 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 µg/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.

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