Distribution of Venlafaxine, O-desmethylvenlafaxine, and O-desmethylvenlafaxine to Venlafaxine Ratio in Postmortem Human Brain Tissue

• Published in: Journal of forensic sciences Vol. 59; no. 3; pp. 683 - 689
• Main Authors: Murrell, Meredith D., Cruz, Dianne A., Javors, Martin A., Thompson, Peter M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2014; Wiley Subscription Services, Inc
• Subjects: Adult; antidepressants; Autopsies; Brain; Brain Chemistry; brain tissue; Chromatography, Liquid; Cyclohexanols - analysis; Cyclohexanols - pharmacokinetics; Desvenlafaxine Succinate; Female; Forensic pathology; forensic science; high-pressure liquid chromatography-ultraviolet detection; Humans; Male; Metabolites; Middle Aged; Postmortem Changes; Psychotropic drugs; Serotonin Uptake Inhibitors - analysis; Serotonin Uptake Inhibitors - pharmacokinetics; toxicology; venlafaxine; Venlafaxine Hydrochloride; toxicology; forensic science; brain tissue; antidepressants; venlafaxine; high-pressure liquid chromatography-ultraviolet detection
• ISSN: 0022-1198; 1556-4029
• DOI: 10.1111/1556-4029.12393

Venlafaxine (VEN) and its metabolite O‐desmethylvenlafaxine (ODV) inhibit reuptake of serotonin and norepinephrine. This study examines whether VEN is differentially distributed in postmortem brain and examines relationships between brain and femoral blood concentrations from donors prescribed VEN for treatment of depression. Using high‐pressure liquid chromatography‐ultraviolet detection, VEN and ODV concentrations were measured in temporal, occipital, and cerebellar cortex of six postmortem brains. The ODV/VEN ratio was calculated as a relative measure of drug metabolism within each region where higher ratios indicated a greater conversion of VEN to ODV. Compared to the other regions examined, the cerebellum showed decreased VEN (p = 0.056), ODV (p = 0.006), and ODV/VEN (p = 0.027) ratios. In parts per million, VEN was higher in temporal and occipital cortex, but not cerebellum, as compared to femoral blood concentration. These observations suggest that VEN and ODV are differentially distributed in the brain, and metabolism of VEN to ODV may vary across brain regions.