Effects of the inhaled corticosteroids fluticasone propionate, triamcinolone acetonide, and flunisolide and oral prednisone on the hypothalamic-pituitary-adrenal axis in adult patients with asthma.
Two multicenter, randomized, double-masked, placebo-controlled, parallel-group studies were conducted in adult patients with mild-to-moderate persistent asthma to assess the effects of 4 weeks of treatment with inhaled corticosteroids on hypothalamic-pituitary-adrenal (HPA) axis function. The first study compared fluticasone propionate 100 and 500 microg twice daily, triamcinolone acetonide 300 and 500 microg twice daily, oral prednisone 10 mg every morning, and placebo. The second study compared fluticasone propionate 100 and 250 microg twice daily, flunisolide 500 microg twice daily, and placebo. Therapeutic doses of fluticasone propionate, triamcinolone acetonide, and flunisolide were found to be comparable to each other and to placebo in their lack of adrenal suppressive effects, based on mean plasma cortisol responses to 6-hour cosyntropin infusion. Prednisone produced significantly greater suppression of HPA-axis function than did any of the inhaled corticosteroids or placebo (P<0.001). Mean reductions from baseline in 8-hour area under the plasma concentration-time curve (AUC) and 8-hour peak plasma cortisol concentrations and the mean percentage of change from baseline in 8-hour AUC were significantly greater after treatment with triamcinolone acetonide 500 microg twice daily compared with placebo (P< or =0.042). These findings indicate that fluticasone propionate has no greater systemic effect than either triamcinolone acetonide or flunisolide at doses appropriate for patients with mild-to-moderate persistent asthma.
Sorkness
C A
CA
University of Wisconsin Hospital and Clinics, Madison 53792, USA.
LaForce
C
C
Storms
W
W
Lincourt
W R
WR
Edwards
L
L
Rogenes
P R
PR
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003366:Cosyntropin / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068298:Fluticasone; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use*
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide; D003366:Cosyntropin; C007734:flunisolide; D000068298:Fluticasone; D014222:Triamcinolone Acetonide; D011241:Prednisone; D006854:Hydrocortisone