A M Wilson1, E J Sims, L C McFarlane, B J Lipworth. 1. Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Scotland.
Abstract
BACKGROUND:Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compared their systemic effects. OBJECTIVE: The purpose of this study was to compare the systemic bioactivity of aqueous formulations of intranasal budesonide, mometasone furoate (MF), and triamcinolone acetonide (TAA) in terms of adrenal, bone, and white blood cell markers. METHODS:Twenty patients with allergic rhinitis, mean age (SE) 35.7 (3.5) years were studied in a single-blind, randomized, 4-way crossover design, with treatments separated by 7-day washout periods, comparing placebo with budesonide 200 micro(g) once daily, MF 200 micro(g) once daily, and TAA 220 micro(g) once daily. After 5 days of treatment at steady-state, serial blood and urine samples were taken for 24 hours. Collective and fractionated measurements (daytime, overnight, and 8 AM) were done on plasma cortisol and urine cortisol/creatinine excretion. Plasma osteocalcin and blood eosinophil counts were measured at 8 AM. RESULTS: There was no significant difference between placebo and the active treatments with any of the markers of adrenal suppression. Mean values (SE) for 24-hour area under the curve plasma cortisol (nmol/L.hr) were placebo, 6312.9 (564.4); budesonide, 5908.8 (496.8); MF, 6374.1 (509.9); and TAA, 6239.2 (552.0). Twenty-four hour urinary cortisol/creatinine ratio (nanomoles per millimoles) showed placebo, 9.2 (0.5); budesonide, 8.5 (0.5); MF, 8.6 (0.4); and TAA, 8.6 (0.4). The diurnal circadian rhythm was unaffected, and there were only occasional patients with abnormally low cortisol values. There was also no suppression in terms of osteocalcin (placebo, 1.27 nmolL; budesonide, 1.22 nmol/L; MF, 1.33 nmol/L; and TAA, 1.24 nmol/L) and blood eosinophil count (placebo, 0.29 x 10(9)/L; budesonide, 0.27 x 10(9)/L; MF, 0.25 x 10(9)/L; and TAA, 0.24 x 10(9)/L). CONCLUSION: Neither budesonide, MF, nor TAA produced significant systemic suppression of adrenal, bone, or white blood cell markers at the doses studied. This reflects the good safety profile of these aqueous intranasal formulations when taken at clinically recommended doses.
RCT Entities:
BACKGROUND: Intranasal corticosteroids are regarded as the first-line treatment for allergic rhinitis, but few studies have directly compared their systemic effects. OBJECTIVE: The purpose of this study was to compare the systemic bioactivity of aqueous formulations of intranasal budesonide, mometasone furoate (MF), and triamcinolone acetonide (TAA) in terms of adrenal, bone, and white blood cell markers. METHODS: Twenty patients with allergic rhinitis, mean age (SE) 35.7 (3.5) years were studied in a single-blind, randomized, 4-way crossover design, with treatments separated by 7-day washout periods, comparing placebo with budesonide 200 micro(g) once daily, MF 200 micro(g) once daily, and TAA 220 micro(g) once daily. After 5 days of treatment at steady-state, serial blood and urine samples were taken for 24 hours. Collective and fractionated measurements (daytime, overnight, and 8 AM) were done on plasma cortisol and urine cortisol/creatinine excretion. Plasma osteocalcin and blood eosinophil counts were measured at 8 AM. RESULTS: There was no significant difference between placebo and the active treatments with any of the markers of adrenal suppression. Mean values (SE) for 24-hour area under the curve plasma cortisol (nmol/L.hr) were placebo, 6312.9 (564.4); budesonide, 5908.8 (496.8); MF, 6374.1 (509.9); and TAA, 6239.2 (552.0). Twenty-four hour urinary cortisol/creatinine ratio (nanomoles per millimoles) showed placebo, 9.2 (0.5); budesonide, 8.5 (0.5); MF, 8.6 (0.4); and TAA, 8.6 (0.4). The diurnal circadian rhythm was unaffected, and there were only occasional patients with abnormally low cortisol values. There was also no suppression in terms of osteocalcin (placebo, 1.27 nmolL; budesonide, 1.22 nmol/L; MF, 1.33 nmol/L; and TAA, 1.24 nmol/L) and blood eosinophil count (placebo, 0.29 x 10(9)/L; budesonide, 0.27 x 10(9)/L; MF, 0.25 x 10(9)/L; and TAA, 0.24 x 10(9)/L). CONCLUSION: Neither budesonide, MF, nor TAA produced significant systemic suppression of adrenal, bone, or white blood cell markers at the doses studied. This reflects the good safety profile of these aqueous intranasal formulations when taken at clinically recommended doses.