Postmortem redistribution mechanism of donepezil in the rat

Recent Periodical Literature:  by Viktor Naumovski

This article details an experiment that tested levels of donepezil in different body parts following death. Alzheimer’s disease is the most common form of dementia in the elderly around the world, characterized by memory impairment and lower cognitive function, is often treated by Donepezil (DPZ) which inhibits acetylcholinesterase.  While trials have shown a high level of safety in using donepezil, excessive doses have led to vomiting, bradycardia, unconsciousness, or even death.  This raises the concern of accidental overdoses as memory impairment and lower cognitive function are symptoms of the disease, increasing the need to have better testing for quantifying donepezil levels found in blood in autopsies during death investigations.  One of the major concerns in testing DPZ following death is that the levels may differ compared to before death due to postmortem redistribution of the drug throughout the body.

Comparisons between the postmortem interval and blood concentration in blood and organs were done in rats at different time intervals postmortem to identify patterns of postmortem redistribution.  For this test, 1mg/mL concentrations of DPZ hydrochloride were made and administered by injection to the rats, given at a dose of 5mg per kg of body weight for 10 days and the rats were sacrificed 3 hours following the last injection, and the rats were left at room temperature for varying hours (0, 1, 3, 6, 12, and 24). Following this samples of blood and various organ tissue samples were taken from each rat and frozen until analysis could be done by mixing with a standard solution and extracted and quantified using high performance liquid chromatography. The results showed a significant increase in DPZ concentration in cardiac blood as time following death increased, and a subsequent decrease in pH levels. Distribution depending on the organ tested showed changes in concentration depending on the hours passed as well, and this information can be adapted to estimate the time passed since the time of death in humans based on the concentrations found in the cardiac blood and the peripheral blood, meaning that blood concentration cannot be solely relied up to identify the cause of death during an autopsy without considering the redistribution patterns.

 Nagasawa, Sayaka, Nobuyuki Katagiri, Akina Nara, Fumiko Chiba, Yuko Kubo, Suguru Torimitsu, Daisuke Yajima, Mamoru Akutsu, and Hirotaro Iwase. “Postmortem Redistribution Mechanism of Donepezil in the Rat.” Forensic Science International 266 (2016): 1-7. Web. doi:10.1016/j.forsciint.2016.04.017

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