131: Intramuscular Triamcinolone Acetonide (Kenalog®): A Conundrum Amongst Corticosteriods

Statement of Purpose: Triamcinolone acetonide is a glucocorticosteroid used in standard clinical practice for its anti-inflammatory properties. Although it can be given via different routes of administration, the intramuscular route is unique compared to other corticosteroids - its effects remain potent over a longer period of time. We summarize existing literature on the pharmacokinetic and pharmacodynamic mechanisms of intramuscular triamcinolone acetonide (Kenalog®).

Description of Methods & Materials: We compiled our research using PubMed’s search engine tool. The following terms were inputted into their search engine tool: “triamcinolone acetonide”, “triamcinolone acetonide potency”, “triamcinolone acetonide intramuscular”, “triamcinolone acetonide pharmacokinetics”, “triamcinolone acetonide intramuscular controlled”. A thorough review of the literature from 1970 onwards was completed and referenced. The UCSF dermatopharmacology-dermatotoxicology library was hand searched.

Data & Results:

The pharmacokinetics of TAC begins at the site of action, where the addition of acetonide allows it to bind very tightly to the glucocorticoid receptor compared to triamcinolone. A similar glucocorticoid, fluocinolone acetonide has been seen to penetrate human skin 14 to 23 times faster than its counterpart, fluocinolone.

In addition to understanding the differences between triamcinolone and triamcinolone acetonide, it is important to evaluate the unique nature of the intramuscular route of administration. Intravenous (IV), intra-articular (IA), and intramuscular routes of administration differ in their pharmacokinetics. Intramuscular and intra-articular triamcinolone acetonide have been previously defined as following a three-compartment model, while intravenous triamcinolone has been defined as following a two-compartment model. 

Triamcinolone converts to several structures during its metabolism to excretion. TAC and some metabolites were identified using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The major metabolite is 6β-hydroxy triamcinolone acetonide (6β-OH-TA, M-I). M-I (6β-OH-TA) was the main metabolite, markedly more present in urine excretions than TA, its parent compound. M-IX (triamcinolone) is considered the minor metabolite compared to M-I (6β-OH-TA). It is important to note, with our minimal understanding of the pharmacokinetics of this drug, that there may be some clinically relevant metabolite that has not yet been identified.

Interpretation, Conclusion or Significance:

Triamcinolone acetonide is consistently used in various specialties via different routes of administration. Although no controlled clinical data exists on the exact mechanism of action for intramuscular triamcinolone acetonide, it is widely clinically accepted as a potent, long-lasting glucocorticoid, beneficial for its immunosuppressive properties. Interestingly, unlike other routes of administration and unlike other glucocorticoids, intramuscular triamcinolone acetonide has a long-lasting effect on the body, as seen in case reports and clinical studies. 

The enigma of triamcinolone acetonide’s purported efficacy may lie in the fact that it has a unique nature of having a long-term effect on the body using a seemingly low dose compared to other routes of administrations and other corticosteroids. Our analysis suggests that this enigma may be attributed to binding differences at the intramuscular site, low solubility due to acetonide esters, slow rate of absorption from the injected site, and low renal clearance rate. There remains much to be learned on the unique properties of this form and use of this drug. Solving this enigma may be of clinical and therapeutic significance.

Disclosures: The authors have no conflicts of interest to disclose.