Document Detail


Prolonged toxicity after amitriptyline overdose in a patient deficient in CYP2D6 activity.
MedLine Citation:
PMID:  21614669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Amitriptyline and its metabolite, nortriptyline, are metabolized, in part, by CYP2D6, a polymorphic enzyme. About 8% of Caucasians are deficient in CYP2D6 activity.
CASE REPORT: We present the case of a comatose woman who intentionally overdosed on amitriptyline and displayed rising serum total tricyclic antidepressant concentrations for at least 6 days after admission. Serial immunoassay total tricyclic antidepressant concentrations in our patient showed gradual decline beginning day 7, although the patient did not regain normal mental status until day 12. Genotyping revealed the patient to be homozygous for the CYP2D6*4 allele, the most common explanation of CYP2D6 enzymatic deficiency among Caucasians. Patients taking tricyclic antidepressants who are homozygous for CYP2D6*4 demonstrate >3 times concentration-time curve (AUCs) and prolonged elimination half-lives, especially of secondary amines such as nortriptyline.
DISCUSSION: We believe this is the first report describing toxicokinetics after tricyclic antidepressant overdose in a CYP2D6-deficient patient.
Authors:
Jennifer Cohen Smith; Steven C Curry
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Journal of medical toxicology : official journal of the American College of Medical Toxicology     Volume:  7     ISSN:  1937-6995     ISO Abbreviation:  J Med Toxicol     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-08     Completed Date:  2011-11-30     Revised Date:  2013-07-31    
Medline Journal Info:
Nlm Unique ID:  101284598     Medline TA:  J Med Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  220-3     Citation Subset:  IM    
Affiliation:
Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, AZ, USA.
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MeSH Terms
Descriptor/Qualifier:
Alprazolam / poisoning
Amitriptyline / blood,  poisoning*
Antidepressive Agents, Tricyclic / blood,  poisoning*
Body Temperature / drug effects
Brain / pathology
Coma / chemically induced
Cytochrome P-450 CYP2D6 / deficiency*,  genetics
Drug Overdose
Electrocardiography
Female
Gas Chromatography-Mass Spectrometry
Genotype
Half-Life
Hemodynamics / physiology
Humans
Hypnotics and Sedatives / poisoning
Magnetic Resonance Imaging
Middle Aged
Respiration, Artificial
Suicide, Attempted
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Tricyclic; 0/Hypnotics and Sedatives; 28981-97-7/Alprazolam; 50-48-6/Amitriptyline; EC 1.14.14.1/Cytochrome P-450 CYP2D6
Comments/Corrections

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


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