Postmortem femoral venous blood concentrations, redistribution and toxicity of duloxetine

Duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is widely prescribed for depression, anxiety, neuropathic pain, and other chronic pain conditions. Its pharmacokinetics show substantial interindividual variability due to sex, age, smoking, and CYP2D6 metabolism. Postmortem (PM) interpretation is further complicated by unknown blood-to-plasma distribution and significant postmortem redistribution. This study analyzed duloxetine concentrations in 2006-2026 Finnish forensic cases (N = 798), including fatal poisonings, polysubstance intoxications, and incidental findings. The median PM concentration of femoral venous blood samples was 0.16 mg/L, close to the upper therapeutic range of clinical plasma samples, while the mean concentration (0.33 mg/L) was twice as high. Based on our studies and data from the literature, toxic concentrations began at approximately 0.6 mg/L and fatal concentrations at 1-2 mg/L. In 13 fatal duloxetine poisonings, concentrations ranged from 0.46 to 9 mg/L, representing suicides and accidental over-dosing. In cases with both antemortem (AM) and PM samples, PM levels were on average 110% higher, indicating slight redistribution. Drug-drug interactions involving CYP2D6 inhibitors or substrates were present in several cases but did not fully explain the highest duloxetine concentrations. These findings highlight the need for cautious interpretation of PM duloxetine levels, especially in polysubstance intoxications and in individuals with impaired metabolism.