title: Prolonged toxicity after amitriptyline overdose in a patient deficient in CYP2D6 activity.
abstract: BACKGROUND
  Amitriptyline and its metabolite, nortriptyline, are metabolized, in part, by CYP2D6, a polymorphic enzyme. About 8% of Caucasians are deficient in CYP2D6 activity.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  We believe this is the first report describing toxicokinetics after tricyclic antidepressant overdose in a CYP2D6-deficient patient.
authors: Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, AZ, USA.
authors: Jennifer Cohen
authors: JC
authors: Smith
authors: Steven C
authors: SC
authors: Curry
references: Ther Drug Monit. 2003 Apr;25(2):248-51
references: 12657923
references: Eur J Clin Pharmacol. 1982;23(6):513-21
references: 7160420
references: Clin Pharmacokinet. 1993 Jun;24(6):453-71
references: 8513649
references: Pharmacology. 1997 Nov;55(5):235-43
references: 9399333
references: Lancet. 1981 Mar 7;1(8219):560-1
references: 6111662
references: Pharmacol Rev. 2006 Sep;58(3):521-90
references: 16968950
references: J Pharmacol Exp Ther. 1994 Nov;271(2):860-7
references: 7965806
references: Clin Pharmacol Ther. 1983 Mar;33(3):360-6
references: 6825390
references: J Toxicol Environ Health B Crit Rev. 2009;12(5-6):334-61
references: 20183526
references: Emerg Med J. 2001 Jul;18(4):236-41
references: 11435353
references: Clin Pharmacol Ther. 1977 Jan;21(1):47-51
references: 832448
references: Drug Metab Dispos. 1997 Jun;25(6):740-4
references: 9193876