title: Clinical and pharmacological aspects of accidental triamcinolone acetonide overdosage: a case study.
abstract: 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.
authors.affiliation: Central Hospital Pharmacy, The Hague, The Netherlands.
authors.forename: D H
authors.initials: DH
authors.lastname: Schweitzer
authors.forename: P P
authors.initials: PP
authors.lastname: Le-Brun
authors.forename: S
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: H
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002062:Bursitis / Q000188:drug therapy; D003480:Cushing Syndrome / Q000139:chemically induced* / Q000188:drug therapy; D062787:Drug Overdose; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D007270:Injections, Intra-Articular; D008508:Medication Errors; D008875:Middle Aged; D015735:Mifepristone / Q000627:therapeutic use; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000893:Anti-Inflammatory Agents; D006727:Hormone Antagonists; D015735:Mifepristone; D014222:Triamcinolone Acetonide