A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration

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 environment ally friendly hydroflurocarbon propellants and breath-actuated dry-powder i nhalers. The purpose of this study was to compare the single- and multiple- dose pharmacokinetics, pharmacodynamics, and tolerability of a newly develo ped hydroflurocarbon formulation of triamcinolone acetonide (Azmacort(R) HF A 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of bude sonide (Pulmicort(R) Turbuhaler 200 mcg). This three-way crossover study us ed I 6 normal healthy subjects each receiving a 675 meg dose of triamcinolo ne acetonide, 600 meg dose of budesonide, or placebo twice a day for 5 days . Serial plasma samples were collected after the first and last dose of tes t medication for pharmacokinetic analysis. Pharmacodynamics were assessed b y changes in hypothalamic-pituitory-adrenal axis function as measured by 8 a.m. serum cortisol, 24-fiour overnight serum cortisol AUC((0.24)) and 24-h our urinary-free cortisol after the last evening dose of test drug. Tolerab ility was assessed through physical examinations, vital signs, 12-lead EGG, routine clinical labs, and adverse events recording. Both compounds were s ystemically absorbed. However, no significant drug accumulation was noted w ith chronic dosing. Chronic dosing did result in a statistically significan t 20% reduction in basal 24-hour serum cortisol AUC((0.24)) for both compou nds. There were no clinically significant abnormalities in physical examina tion, vital signs, 12-lead EGG, or routine clinical labs noted during the s tudy. Overall, the study drugs were well tolerated, with adverse events cha racterized as mild to moderate in severity. (C) 2000 the American College o f Clinical Pharmacology.