Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis

• Published in: Journal of allergy and clinical immunology 1998-08, Vol.102 (2), p.191-197
• Main Authors: Vargas, Ramón, Dockhorn, Robert J., Findlay, Steven R., Korenblat, Phillip E., Field, Elizabeth A., Kral, Kenneth M.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Administration, Oral; Administration, Topical; Adolescent; Adult; Aerosols; Aged; Androstadienes - adverse effects; Androstadienes - therapeutic use; Anti-Allergic Agents - adverse effects; Anti-Allergic Agents - therapeutic use; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Cosyntropin; Double-Blind Method; Drug toxicity and drugs side effects treatment; Female; Fluticasone; fluticasone propionate; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Humans; Hydrocortisone - blood; Hydrocortisone - urine; Hypothalamo-Hypophyseal System - drug effects; intranasal; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Pituitary-Adrenal System - drug effects; Prednisone - administration & dosage; Prednisone - adverse effects; Prednisone - therapeutic use; Rhinitis, Allergic, Perennial - blood; Rhinitis, Allergic, Perennial - drug therapy; Rhinitis, Allergic, Perennial - urine; Rhinitis, Allergic, Seasonal - blood; Rhinitis, Allergic, Seasonal - drug therapy; Rhinitis, Allergic, Seasonal - urine
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(98)70085-5

Background: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. Objective: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)–axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. Methods: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 μg once daily, FP ANS 400 μg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily , or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. Results: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 μg once daily or FP ANS 400 μg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant ( p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration–time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 μg twice daily and both prednisone regimens were associated with a significant ( p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. Conclusion: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test. (J Allergy Clin Immunol 1998;102:191-7.)