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Mechanism of Action
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs such as prednisolone and triamcinolone are primarily used for their anti-inflammatory effects in disorders of many organ systems. Triamcinolone acetonide possesses glucocorticoid activity typical of this class of drug, but with little or no mineralocorticoid activity. For the purposes of comparison, the following is the equivalent milligram dosage of the various glucocorticoids:
|Cortisone, 25||Prednisone, 5||Paramethasone, 2|
|Hydrocortisone, 20||Methylprednisolone, 4||Betamethasone, 0.75|
|Prednisolone, 5||Triamcinolone, 4||Dexamethasone, 0.75|
Corticosteroids have been demonstrated to depress the production of eosinophils and lymphocytes, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.
Aqueous humor pharmacokinetics of triamcinolone have been assessed in 5 patients following a single intravitreal administration (4 mg) of triamcinolone acetonide. Aqueous humor samples were obtained from 5 patients (5 eyes) via an anterior chamber paracentesis on Days 1, 3, 10, 17 and 31 post injection. Peak aqueous humor concentrations of triamcinolone ranged from 2151 to 7202 ng/mL, half-life 76 to 635 hours, and the area under the concentration-time curve (AUC0-t) from 231 to 1911 ng.h/mL following the single intravitreal administration. The mean elimination half-life was 18.7 ± 5.7 days in 4 nonvitrectomized eyes (4 patients). In a patient who had undergone vitrectomy (1 eye), the elimination half-life of triamcinolone from the vitreous was much faster (3.2 days) relative to patients that had not undergone vitrectomy.
Animal Toxicology and/or Pharmacology
Studies were conducted with triamcinolone acetonide, including those employing the proposed dosage form, i.e., 4.0% triamcinolone acetonide injectable suspension formulation containing 0.5% carboxymethylcellulose and 0.015% polysorbate-80 in a balanced salt solution.
Triamcinolone acetonide was demonstrated to be non-inflammatory when injected intravitreally in NZW rabbits, non-cytotoxic to mouse L-929 cells in an in-vitro assay and non-sensitizing in a guinea-pig maximization assay. Furthermore, the results of single-dose intravitreal injection studies with triamcinolone acetonide in both rabbits and monkeys demonstrate that the drug is well tolerated for up to one month with only minor findings of slight decrease in body weight gain and slight corneal thinning.
Last reviewed on RxList: 10/5/2009
This monograph has been modified to include the generic and brand name in many instances.
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