Flunisolide

T B Casale, MD(*); H S Nelson, MD; W Stricker, MD; J A Fourre, MD and K B Newman, MD. Medicine, Creighton University, Omaha, NE; Medicine, National Jewish Medical and Research Center, Denver, CO; Forest Labs, New York, NY and Forest Labs, New York, NY.

PURPOSE: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a marker of systemic absorption of corticosteroids. We studied the temporal pattern of HPA suppression associated with the inhaled corticosteroids-flunisolide and fluticasone propionate in patients with mild-to-moderate asthma.

METHODS: A total of 153 patients were randomly assigned to receive flunisolide (500 g and 1000 g bid), fluticasone propionate (110, 220, 330, or 440 g bid), prednisone (7.5 mg qd), or placebo for 21 days. Serial measurement of serum cortisol was used to monitor drug-associated HPA axis suppression at baseline and on day 21. Beginning at 10 pm, blood samples were drawn every 2 hours for 22 hours.

RESULTS: Dose-related suppression of cortisol in patients receiving fluticasone propionate was significantly greater than in patients receiving flunisolide. The diurnal pattern of cortisol suppression associated with fluticasone propionate differed from that of flunisolide. Relative to baseline, serum cortisol measurements on day 21 revealed a persistent, unremitting pattern of cortisol suppression throughout the day in patients receiving high doses of fluticasone propionate. The pattern was similar to that observed in patients receiving oral prednisone. In patients receiving high-dose flunisolide, cortisol suppression was primarily restricted to die hours 10 pm to 4 am and noon to 4pm, without any cortisol suppression observed during the 8 am daily peak of cortisol secretion. However, in patients receiving fluticasone propionate 440 g bid, mean 8 am cortisol concentrations were significantly suppressed. This may be a reflection of the longer serum half-life of fluticasone propionate as compared to flunisolide.

CONCLUSION: In adult patients with mild-to-moderate asthma, significantly, greater HPA axis suppression occurs with inhaled fluticasone propionate than with flunisolide. Furthermore, the pattern of suppression was different between the 2 drugs, with fluticasone propionate causing cortisol suppression throughout the entire day.

CLINICAL IMPLICATIONS: The clinical implications of these findings should be further investigated.

COPYRIGHT 2000 American College of Chest Physicians
COPYRIGHT 2001 Gale Group