title: 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?
abstract: The present study was undertaken to describe the pharmacokinetics of a new solution-based intranasal triamcinolone acetonideformulation (Tri-Nasal) 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 microg) 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 microg. 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 microg of the solution-based and suspension-based formulations, respectively. In summary, based on the results of this PK/PD simulation, the plasma levels observed afternasal administration of the solution or the aqueous suspension are unlikely to induce a clinically relevant cortisol suppression, especially for the recommended dosing regimens of 200 and 220 microg/day.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
authors.forename: Günther
authors.initials: G
authors.lastname: Hochhaus
authors.forename: Mario A
authors.initials: MA
authors.lastname: González
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Dockhorn
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shilstone
authors.forename: John
authors.initials: J
authors.lastname: Karafilidis
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D013535:Suspensions; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D013535:Suspensions; D014222:Triamcinolone Acetonide; D006854:Hydrocortisone