The impending phaseout of
chlorofluorocarbons as propellants in pressurized
metered-dose inhalers used in the treatment of
asthma has resulted in the development of alternative devices to deliver
drug to the pulmonary airways. These alternative devices include
metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated
dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of
triamcinolone acetonide (
Azmacort HFA 225 mcg Inhalation
Aerosol) to that of the dry-
powder formulation of
budesonide (
Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of
triamcinolone acetonide, 600 mcg dose of
budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum
cortisol, 24-hour overnight serum
cortisol AUC(0-24), and 24-hour urinary-free
cortisol after the last evening dose of test
drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant
drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum
cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.