Distribution of venlafaxine in three postmortem cases

Area of Science:

• Forensic Toxicology
• Pharmacology
• Analytical Chemistry

Background:

• Venlafaxine (V), a second-generation antidepressant, inhibits norepinephrine and serotonin reuptake.
• Its primary elimination pathways are O- and N-demethylation, producing the active metabolite O-desmethylvenlafaxine (ODV).
• Therapeutic concentrations are approximately 0.2 mg/L for V and 0.4 mg/L for ODV.

Observation:

• Three cases of venlafaxine (V) intoxication are presented.
• Gas chromatography-nitrogen-phosphorus detection and gas chromatography-mass spectrometry were used to identify and quantify V and ODV in biological specimens.
• High concentrations of V and ODV were found in heart blood: (6.6, 31), (84, 15), and (44, 50) mg/L.

Findings:

• Venlafaxine and O-desmethylvenlafaxine were successfully identified and quantified in postmortem toxicology.
• Elevated levels of V and ODV were detected in all three cases of fatal drug intoxication.
• Co-ingestions of other substances, including acetaminophen, diphenhydramine, amitriptyline, nortriptyline, and chlordiazepoxide, were also identified.

Implications:

• This study highlights the potential for severe toxicity and lethality with venlafaxine overdose.
• Accurate toxicological analysis is crucial for determining the role of venlafaxine in drug-related deaths.
• Understanding venlafaxine's metabolism and toxicokinetics is vital for clinical and forensic settings.