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Institute of Pharmacology, Pharmacy and Toxicology, University of Leipzig, An den Tierkliniken 15, D-04103 Leipzig, Germany
(Requests for offprints should be addressed to G Abraham; Email: gabraham{at}rz.uni-leipzig.de)
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-
-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 (1315 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, 0.61.5 h) and low maximum plasma concentrations (peak Cmax, 2.995.51 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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