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 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.
Argenti
D
D
Aventis Pharmaceuticals, U.S. Medical Affairs-Clinical Pharmacology and Pharmacokinetics, Collegeville, Pennsylvania 19426, USA.
Shah
B
B
Heald
D
D
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants / Q000008:administration & dosage; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D019819:Budesonide / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage*; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D009330:Nebulizers and Vaporizers; D011674:Pulse; D014222:Triamcinolone Acetonide / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents; D019819:Budesonide; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; D014222:Triamcinolone Acetonide; C094049:apaflurane; D005466:Fluorocarbons