Adrenal suppression with high doses of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers

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Abstract
Study objective: This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers, both given via their respective pressurised metered dose inhaler (pMDI) devices at high doses within the manufacturers recommended dose range. Design: We used a single (investigator) blind, randomised, crossover design comparing a total daily dose of 1.625 mg fluticasone propionate delivered via a pMDI, 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer, or placebo pMDI; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period. Each drug treatment was separated by a 1-week washout. Patients: Twelve normal subjects mean age 27.5 years were studied. Measurements: Blood samples were taken for 0800 hours plasma cortisol, i.e. 10 h following the second dose. Ten hour urine collections (2200 hours until 0800 hours) were taken for urinary cortisol and creatinine excretion. Results: For the 0800 hours plasma cortisol (geometric mean, nmol · l−1) compared with placebo (353) fluticasone propionate (138) produced significant (P−1 (n=4 for fluticasone propionate and n=0 for triamcinolone acetonide. Overnight urinary cortisol/creatinine ratio (geometric mean, nmol/mmol) did not show any difference between fluticasone propionate (1.48) and triamcinolone acetonide (1.60), with both producing significant suppression versus placebo (4.01): triamcinolone acetonide 2.50-fold difference (95% CI 1.45–4.24); fluticasone propionate 2.71-fold difference (95% CI 1.57–4.69). Conclusion: Fluticasone propionate 1.625 mg/day (pMDI) produced an approximately two-fold greater adrenal suppression of 0800 hours plasma cortisol than triamcinolone acetonide 1.60 mg per day (Oral Inhaler) when given twice daily, and one third of subjects with fluticasone had abnormally low 0800 hours cortisol values −1 (−1). There were no differences between the drugs for urinary cortisol excretion. Further dose-ranging studies are required at steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose–response curve for both plasma and urinary cortisol suppression.

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