Postmortem tissue concentrations of venlafaxine

Venlafaxine is a phenethylamine antidepressant which inhibits both serotoni n and norepinephrine reuptake and is structurally unrelated to the serotoni n reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytoc hrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far les ser extent than do the SSRIs. Mechanisms of drug action are reviewed and ev aluated in the investigation of 12 fatalities occurring over a 6-month-peri od where venlafaxine was detected. Venlafaxine and ODV were identified by liquid chromatography-in ass spectro metry (LC-MS) using atmospheric pressure ionization (API) electrospray in p ositive mode following an n-butyl chloride extraction. Postmortem tissue co ncentrations studied in each of 12 postmortem cases for venlafaxine and ODV , were 0.1-36 and <0.05-3.5 mg/l (peripheral blood), <0.05-22 and <0.05-9.9 mg/kg (liver), <0.05-10 and <0.05-1.5 mg/l (vitreous), <0.05-53 and <0.05- 6.8 mg/l (bile), <0.05-55 and <0.05-21 mg/l (urine), respectively, and 0.1- 200 mg of venlafaxine in the gastric contents. Venlafaxine was typically pr esent with other drugs, including other antidepressants, alcohol, and benzo diazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.