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

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-aacetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific timedependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13-15 and O120 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 (t max , 0 . 6-1 . 5 h) and low maximum plasma concentrations (peak C max , 2 . . 51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13 . 9G1 . 3 h) was very much shorter than that of TAA (125 . 9G15 . 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.

Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies

“…Screening should therefore be timed, if possible, at least 1 week after the exogenous glucocorticoid has been tapered to a physiological dose or removed. 13 Prolonged released formulations (intra-articular and epidural, especially triamcinolone), cause low level cortisol and a blunted response to ACTH stimulation for 4-6 weeks, outside of CYP3A4 inhibition 41,42 and likely for longer with it. Test results need to be interpreted with caution and with endocrinology input.…”

Review of glucocorticoid therapy in horses. Part 1: Pharmacology

“…; Abraham et al . ; Bentz ). Parenteral triamcinolone acetonide has been used in the past for treatment of systemic diseases such as RAO (Lapointe et al .…”

Particulate versus non-particulate steroids for lumbar transforaminal or interlaminar epidural steroid injections: an update

“…It was hypothesized that particulate steroid preparations may provide a local depot effect with constant release of the active drug from the administration site over a longer time period compared to non-particulate steroids [53].…”

“…The duration of action of intramuscular administered triamcinolone acetonide representing a particulate glucocorticoid was studied in an investigation with dogs and compared to intravenous administered triamcinolone acetonide dihydrogen phosphate (TAA-DHP), which represents the non-particulate steroid [53]. It was shown that a single dose of the particulate glucocorticoid (triamcinolone acetonide) after intramuscular administration revealed a much longer duration of action of up to 4 weeks on the hypothalamicpituitary-adrenal axis activity in dogs than a similar intravenous dose of its analogue, the non-particulate steroid (TAA-DHP) [53].…”

“…It was shown that a single dose of the particulate glucocorticoid (triamcinolone acetonide) after intramuscular administration revealed a much longer duration of action of up to 4 weeks on the hypothalamicpituitary-adrenal axis activity in dogs than a similar intravenous dose of its analogue, the non-particulate steroid (TAA-DHP) [53]. The duration of action of the intravenous nonparticulate steroid (TAA-DHP) was only up to 72 h [53], although the potentially longer duration of action of intramuscular administered TAA-DHP was not evaluated in this study.…”