Document Detail


Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.
MedLine Citation:
PMID:  9068197     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In two unrelated cases, a 7-year-old boy and a 21-year-old woman died suddenly while receiving chronic imipramine therapy. In the boy, concentrations of imipramine were: Left femoral blood 0.5 mg/L, right femoral blood 1.2 mg/L, aorta blood 1.0 mg/L, liver 68 mg/Kg, and for the active metabolite, desipramine, left femoral blood 6.7 mg/L, right femoral blood 9.9 mg/L, aorta blood 8.7 mg/L, liver 400 mg/Kg. In the woman, the imipramine concentrations were: Femoral blood 0.6 mg/L, liver 37 mg/Kg, and of the active metabolite, desipramine, femoral blood 3.74 mg/L, liver 261 mg/Kg. In both cases, the scene investigation strongly indicated that neither individual had ingested an acute overdose. The very high ratios of desmethyl metabolite to parent drug are consistent with this observation. Impaired metabolism due to a genetically determined "slow metabolizer" phenotype of cytochrome CYP2D6, and/or concurrent therapy with phenothiazines, is suggested as a possible mechanism for the apparent fatal accumulation of these tricyclic antidepressants.
Authors:
J R Swanson; G R Jones; W Krasselt; L N Denmark; F Ratti
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of forensic sciences     Volume:  42     ISSN:  0022-1198     ISO Abbreviation:  J. Forensic Sci.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-09     Completed Date:  1997-04-09     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0375370     Medline TA:  J Forensic Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  335-9     Citation Subset:  IM    
Affiliation:
Pathology Department, Oregon Health Sciences University, Portland, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antidepressive Agents, Tricyclic / adverse effects*,  metabolism,  therapeutic use
Child
Death, Sudden / etiology*
Desipramine / adverse effects*,  metabolism
Female
Humans
Imipramine / adverse effects*,  metabolism,  therapeutic use
Male
Time Factors
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Tricyclic; 50-47-5/Desipramine; 50-49-7/Imipramine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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