Triamcinolone acetonide is a more potent derivative of triamcinolone. Although triamcinolone itself is approximately one to two times as potent as prednisone in animal models of inflammation, triamcinolone acetonide is approximately 8 times more potent than prednisone.

Although the precise mechanism of corticosteroid antiallergic action is unknown, corticosteroids are very effective. However, when allergic symptoms are very severe, local treatment with recommended doses (microgram) of any available topical corticosteroid is not as effective as treatment with larger doses (milligram) of oral or parenteral formulations.

Based upon intravenous dosing of triamcinolone acetonide phosphate ester in adults, the half-life of triamcinolone acetonide was reported to be 88 minutes. The volume of distribution (Vd) reported was 99.5 L (SD ± 27.5) and clearance was 45.2 L/hour (SD ± 9.1) for triamcinolone acetonide. The plasma half-life of corticosteroids does not correlate well with the biologic half-life.

Pharmacokinetic characterization of the Nasacort AQ Nasal Spray formulation was determined in both normal adult subjects and patients with allergic rhinitis. Single dose intranasal administration of 220 mcg of Nasacort AQ Nasal Spray in normal adult subjects and patients demonstrated minimal absorption of triamcinolone acetonide. The mean peak plasma concentration was approximately 0.5 ng/mL (range: 0.1 to 1.0 ng/mL) and occurred at 1.5 hours post dose. The mean plasma drug concentration was less than 0.06 ng/mL at 12 hours, and below the assay detection limit at 24 hours. The average terminal half-life was 3.1 hours. The range of mean AUC0–∞ values was 1.4 ng•hr/mL to 4.7 ng•hr/mL between doses of 110 mcg to 440 mcg in both patients and healthy volunteers. Dose proportionality was demonstrated in both normal adult subjects and in allergic rhinitis patients following single intranasal doses of 110 mcg or 220 mcg Nasacort AQ Nasal Spray. The Cmax and AUC of the 440 mcg dose increased less than proportionally when compared to 110 and 220 mcg doses. Following multiple doses in pediatric patients receiving 440 mcg/day, plasma drug concentrations, AUC, Cmax and Tmax were similar to those values observed in adult patients.

In animal studies using rats and dogs, three metabolites of triamcinolone acetonide have been identified. They are 6β-hydroxytriamcinolone acetonide, 21-carboxytriamcinolone acetonide and 21-carboxy-6β-hydroxytriamcinolone acetonide. All three metabolites are expected to be substantially less active than the parent compound due to (a) the dependence of anti-inflammatory activity on the presence of a 21-hydroxyl group, (b) the decreased activity observed upon 6-hydroxylation, and (c) the markedly increased water solubility favoring rapid elimination. There appeared to be some quantitative differences in the metabolites among species. No differences were detected in metabolic pattern as a function of route of administration.

In order to determine if systemic absorption plays a role in Nasacort AQ's treatment of allergic rhinitis symptoms, a two week double-blind, placebo-controlled clinical study was conducted comparing Nasacort AQ, orally ingested triamcinolone acetonide, and placebo in 297 adult patients with seasonal allergic rhinitis. The study demonstrated that the therapeutic efficacy of Nasacort AQ Nasal Spray can be attributed to the topical effects of triamcinolone acetonide.

In order to evaluate the effects of systemic absorption on the Hypothalamic-Pituitary-Adrenal (HPA) axis, a clinical study was performed in adults comparing 220 mcg or 440 mcg Nasacort AQ per day, or 10 mg prednisone per day with placebo for 42 days. Adrenal response to a six-hour cosyntropin stimulation test showed that Nasacort AQ administered at doses of 220 mcg and 440 mcg had no statistically significant effect on HPA activity versus placebo. Conversely, oral prednisone at 10 mg/day significantly reduced the response to ACTH.

A study evaluating plasma cortisol response thirty and sixty minutes after cosyntropin stimulation in 80 pediatric patients who received 220 mcg or 440 mcg (twice the maximum recommended daily dose) daily for six weeks was conducted. No abnormal response to cosyntropin infusion (peak serum cortisol < 18 mcg/dL) was observed in any pediatric patient after six weeks of dosing with Nasacort AQ at 440 mcg per day.

Clinical Trials

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