Clinical and pharmacological aspects of accidental triamcinolone acetonide overdosage: a case study

Local administration of corticosteroids for rheumatic diseases have had a long history of effective and well-tolerated use. We report here the pharmacodynamics and pharmacokinetics of an accidental triamcinolone acetonide (TCA) overdose. The presented patient was treated with 200 mg TCA and developed Cushing's syndrome 6 weeks later (cortisol and ACTH concentrations were below limits of detection, TCA concentrations were > 3 micrograms/l). Because of her severe symptoms, mifepristone was administered for a period of 19 days. Cortisol concentrations became detectable 2 days after initiation of mifepristone treatment and persisted, being detectable for a period of at least a week after cessation of the drug. Twenty days after cessation, cortisol concentrations were undetectable again. Cushing's syndrome persisted more than 6 months while TCA concentrations remained detectable for at least 80 days. Based on plasma TCA concentrations in our patient, we calculated a terminal half-life of TCA of 33 days as opposed to 5 days observed after intra-articular administration of a therapeutic dose of 40 mg TCA. We conclude that after an accidental overdose in this patient, body TCA disappearance was strongly prolonged due to a very slow (absorption) half-life of the drug in comparison to a therapeutic dose. This finding is explained by a 'flap-flop phenomenon' where drug absorption is the rate-limiting step of overall drug disposition. Caution is, therefore, needed to prevent undesired accumulation of TCA that may lead to protracted Cushing's syndrome.