cosyntropin and flunisolide

Inhaled corticosteroids are established as maintenance therapy for persistent asthma. A new aerosol formulation of flunisolide delivers a small particle size by using a hydrofluoroalkane (HFA) propellant with a built-in spacer.. To compare efficacy and safety of two different flunisolide formulations, HFA and chlorofluorocarbon (CFC), with placebo treatment over a range of doses.. The multicenter, randomized, double-blind, placebo-controlled trial consisted of a 2-week, active run-in phase with CFC flunisolide 500 microg, twice daily, followed by 12 weeks of double-blind treatment with placebo, HFA flunisolide (85, 170, or 340 microg, twice daily), or CFC flunisolide (250, 500, or 1,000 microg, twice daily). Patients (N = 669) were nonsmokers, at least 12 years of age, with mild to moderate asthma who were being treated with inhaled corticosteroids. Outcome measures were change from baseline in forced expiratory volume in 1 second (FEV1), peak expiratory flow rate, as needed albuterol use, nocturnal awakenings, and asthma symptoms.. After 12 weeks of treatment, patients receiving 170 microg, twice daily, and 340 microg, twice daily, of HFA flunisolide showed a significant (P < 0.01) improvement in percentage increase in FEV1 (12.22% at 170 microg, twice daily, and 14.69% at 340 microg, twice daily) compared with the placebo group (5.35%). At one-third the dose of CFC flunisolide, HFA flunisolide provided similar improvement in pulmonary function versus placebo. Both formulations demonstrated comparable linear dose dependency for the change from baseline in FEV1 without any evidence of cortisol suppression. Outcome values for all seven secondary efficacy measures were numerically superior in patients receiving HFA flunisolide compared with the CFC formulation. Both formulations seemed to be safe and well tolerated.. HFA flunisolide provides comparable efficacy and safety at one-third the dose of CFC flunisolide.

Topics: Administration, Inhalation; Adrenal Glands; Adult; Aerosol Propellants; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Cosyntropin; Dose-Response Relationship, Drug; Female; Fluocinolone Acetonide; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Particle Size; Peak Expiratory Flow Rate

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.

Topics: Administration, Inhalation; Administration, Oral; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Area Under Curve; Asthma; Cosyntropin; Double-Blind Method; Female; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Prednisone; Triamcinolone Acetonide

The purpose of this study was to compare the effectiveness of flunisolide aerosol prescribed as .5 mg (two inhalations) twice daily and placebo in terms of oral steroid sparing ability in a population of 32 known steroid-dependent children and adolescents. Patients were stabilized on the lowest tolerated dose of daily AM or alternate AM oral corticosteroid for at least one month before entering the study. They were randomly assigned to either flunisolide or placebo treatment for the 12-week, double-blind trial. Patients were seen every two weeks for symptom assessment, physical examination, and pulmonary function testing. Tests of adrenal function were done initially and at the study's conclusion. The flunisolide group had improved asthma control compared with the placebo group. The daily oral steroid requirement decreased in 100 percent of the flunisolide group compared with 53 percent of the placebo group (P less than .01). Pulmonary function and endocrine function remained stable for both groups. There were no adverse effects. Flunisolide aerosol in doses of .5 mg twice daily appears to be topically active and to have oral steroid potential without apparent adverse effects.

Topics: Adolescent; Aerosols; Aging; Asthma; Child; Child, Preschool; Clinical Trials as Topic; Cosyntropin; Double-Blind Method; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Placebos; Respiratory Function Tests; Steroids; Time Factors