Clinical and pharmacological aspects of accidental triamcinolone acetonideoverdosage: a case study

Local administration of corticosteroids for rheumatic diseases have had a l ong history of effective and well-tolerated use. We report here the pharmac odynamics and pharmacokinetics of an accidental triamcinolone acetonide (TC A) overdose. The presented patient was treated with 200 mg TCA and develope d Cushing's syndrome 6 weeks later (cortisol and ACTH concentrations were b elow limits of detection, TGA concentrations were >3 mu g/l) Because of her severe symptoms, mifepristone was administered for a period of 19 days. Co rtisol concentrations became detectable 2 days after initiation of mifepris tone treatment and persisted, being detectable for a period of at least a w eek after cessation of the drug. Twenty days after cessation, cortisol conc entrations 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 termina l half-life of TGA of 33 days as opposed to 5 days observed after intra-art icular administration of a therapeutic dose of 40 mg TCA. We conclude that after an accidental overdose in this patient, body TCA disappearance was st rongly prolonged due to a very slow (absorption) half-life of the lug in co mparison to a therapeutic dose. This finding is explained by a 'flip-flop p henomenon' where drug absorption is the rate-limiting step of overall drug disposition. Caution is, therefore, needed to prevent undesired accumulatio n of TCA that may lead to protracted Cushing's syndrome. (C) 2000 Elsevier Science B.V. All rights reserved.