A New Solution-Based Intranasal Triamcinolone Acetonide Formulation in Patients with Perennial Allergic Rhinitis: How Does the Pharmacokinetic/Pharmacodynamic Profile for Cortisol Suppression Compare with an Aqueous Suspension-Based Formulation?

• Published in: Journal of clinical pharmacology 2002-06, Vol.42 (6), p.662-669
• Main Authors: Hochhaus, Günther, González, Mario A., Dockhorn, Robert J., Shilstone, Jonathan, Karafilidis, John
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Adult; Area Under Curve; Biological and medical sciences; Cross-Over Studies; Female; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - drug effects; Male; Medical sciences; Pharmacology. Drug treatments; Pituitary-Adrenal System - drug effects; Respiratory system; Rhinitis, Allergic, Perennial - drug therapy; Suspensions; Triamcinolone Acetonide - administration & dosage; Triamcinolone Acetonide - pharmacokinetics; Triamcinolone Acetonide - pharmacology
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00970002042006009

The present study was undertaken to describe the pharmacokinetics of a new solution‐based intranasal triamcinolone acetonide formulation (Tri‐Nasaf®) in patients with perennial allergic rhinitis and to use a pharmacokinetic/pharmacodynamic (PK/PD) simulation approach to compare the potential effects on plasma cortisol with that of an aqueous suspension‐based nasal triamcinolone acetonide formulation (Nasacort® AQ). Data from an open‐label, randomized, three‐way crossover study in patients with perennial allergic rhinitis receiving three doses (100, 200, and 400 μg) of a nasal solution‐based triamcinolone acetonide formulation (Tri‐Nasal®) over 7 days were used to describe the pharmacokinetics of this formulation. Available literature data for a suspension‐based aqueous triamcinolone acetonide formulation (Nasacort® AQ) were used to describe its pharmacokinetic profile after similar single doses of 110, 220, and 440 μg. A PK/PD simulation approach was used to predict the anticipated cumulative cortisol suppression (CCS) of these two formulations. These simulations suggested a cortisol suppression of 8% to 16% for the single and steady‐ state doses of the solution‐based product. Similar CCS estimates were predicted for equivalent doses of the aqueous suspension‐based triamcinolone acetonide formulation with no difference between both formulations. Post hoc power analysis suggested that the predicted cortisol suppression is not likely to be significant for either preparation, including the clinically recommended doses of 200 and 220 μg of the solution‐based and suspension‐based formulations, respectively. In summary, based on the results of this PK/PD simulation, the plasma levels observed after nasal administration of the solution or the aqueous suspension are unlikely to induce a clinically relevant cortisol suppression, especially for the recommended dosing regimens of200 and 220 μg/day.