OBJECTIVES: This study was designed to assess the relationship between the degree of airflow obstruction and the suppression of the hypothalamic-pituitary-adrenal axis after inhalation of fluticasone propionate (FP) in asthmatic patients with varying degrees of airway obstruction. STUDY DESIGN: The nocturnal cortisol production (from 10:00 PM to 6:00 AM), defined as the integrated area under the curve of nocturnal plasma cortisol, was measured following inhalation of a placebo or a single dose of 500 microg FP at 8:00 PM in 28 patients with mild to moderate asthma, in a single, blind, 2-night study. RESULTS: The mean morning rise of cortisol decreased significantly following a single dose of inhaled FP. When the total nocturnal cortisol production after the second night (when the FP was inhaled) was compared to that after the first night (when the placebo was administered), it was found to have decreased by 29.4%. There was a statistically significant correlation between the FEV(1) and the fall in cortisol production just before the inhalation of FP (p < 0. 001). There was no correlation between baseline cortisol production and the fall in cortisol production. CONCLUSIONS: Our findings suggest that the degree of airway obstruction affects the systemic bioavailability of FP. FP is likely to induce a more severe decrease in nocturnal cortisol secretion in less obstructed patients. In order to reduce the risk for systemic side effects, the patient's degree of airway obstruction should be considered when planning inhaled FP treatment.
RCT Entities:
OBJECTIVES: This study was designed to assess the relationship between the degree of airflow obstruction and the suppression of the hypothalamic-pituitary-adrenal axis after inhalation of fluticasone propionate (FP) in asthmatic patients with varying degrees of airway obstruction. STUDY DESIGN: The nocturnal cortisol production (from 10:00 PM to 6:00 AM), defined as the integrated area under the curve of nocturnal plasma cortisol, was measured following inhalation of a placebo or a single dose of 500 microg FP at 8:00 PM in 28 patients with mild to moderate asthma, in a single, blind, 2-night study. RESULTS: The mean morning rise of cortisol decreased significantly following a single dose of inhaled FP. When the total nocturnal cortisol production after the second night (when the FP was inhaled) was compared to that after the first night (when the placebo was administered), it was found to have decreased by 29.4%. There was a statistically significant correlation between the FEV(1) and the fall in cortisol production just before the inhalation of FP (p < 0. 001). There was no correlation between baseline cortisol production and the fall in cortisol production. CONCLUSIONS: Our findings suggest that the degree of airway obstruction affects the systemic bioavailability of FP. FP is likely to induce a more severe decrease in nocturnal cortisol secretion in less obstructed patients. In order to reduce the risk for systemic side effects, the patient's degree of airway obstruction should be considered when planning inhaled FP treatment.
Authors: Kevin J Mortimer; Tim W Harrison; Yufei Tang; Kai Wu; Sarah Lewis; Srikumar Sahasranaman; Gunther Hochhaus; Anne E Tattersfield Journal: Br J Clin Pharmacol Date: 2006-10 Impact factor: 4.335