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  • Title: Comparison of the hypothalamic-pituitary-adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation.
    Author: Abraham G, Demiraj F, Ungemach FR.
    Journal: J Endocrinol; 2006 Nov; 191(2):491-6. PubMed ID: 17088419.
    Abstract:
    The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-alpha-acetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific time-dependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13-15 and > 120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1.5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (tmax, 0.6-1.5 h) and low maximum plasma concentrations (peak Cmax, 2.99-5.51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13.9 +/- 1.3 h) was very much shorter than that of TAA (125.9 +/- 15.8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.
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