A pharmacokinetic study to evaluate the absolute bioavailability of triamcinolone acetonide following inhalation administration.
Triamcinolone acetonide is a glucocorticoid administered by oral inhalation in the management of asthma. With oral inhalation of glucocorticoids, systemic absorption can come from oropharyngeal, gastrointestinal, or airway deposition of the drug. The objectives of this study were to determine the absolute bioavailability of triamcinolone acetonide following inhalation administration and to delineate the airway contribution of triamcinolone acetonide absorption relative to the absolute bioavailability. All subjects received a 5-minute 400 mcg intravenous infusion of triamcinolone acetonide and a single 800 mcg dose of inhaled triamcinolone acetonide with and without oral charcoal administration in a randomized three-way crossover fashion. The oral charcoal allowed for isolating the pulmonary component of absorption by adsorbing the oropharyngeal and gastrointestinal deposited drug. The mean (+/- SD) absolute bioavailability value for inhaled triamcinolone acetonide was 25% (8.75%). Delineation of the airway contribution of triamcinolone acetonide absorption showed that 10.4% of an inhaled dose is absorbed as triamcinolone acetonide from the lungs. Mean (+/- SD) total body clearance was rapid at 0.57 (0.12) L/hr/kg. The mean (+/- SD) apparent volume of distribution following the intravenous dose was a low 1.96 (0.31) L/kg. No significant differences were noted in the apparent terminal elimination half-life of triamcinolone acetonide (approximately 2.4 hr) between treatments.
Rhône-Poulenc Rorer, Medical Affairs-Clinical Pharmacology and Pharmacokinetics, Collegeville, Pennsylvania 19426, USA.
D
D
Argenti
B
B
Shah
D
D
Heald
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010352:Patient Dropouts; D014222:Triamcinolone Acetonide / Q000493:pharmacokinetics*
D005938:Glucocorticoids; D014222:Triamcinolone Acetonide