Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion—a randomized controlled animal poisoning model
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Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.
KeywordsAmitriptyline Poisoning Activated charcoal hemoperfusion Cardiotoxicity UHPLC-MS/MS Tissue concentrations Forensic medicine
The study was supported by the Aase and Ejnar Danielsen Foundation—a general private foundation who supports free medical research. The foundation was not involved in the trial or paper finalizing. The study was supported by the Research Foundation at Bispebjerg University Hospital, Copenhagen. The Research Foundation was not involved in the conduction of the trail or production of the paper.
All authors have contributed throughout the process of this paper. TJ: Tejs Jansen, LCGH: Lotte CG Hoegberg, TE: Thomas Eriksen, KPD: Kim Peder Dalhoff, BB: Bo Belhage, SSJ: Sys S Johansen. TJ, LCCH, TE, KPD and BB conceived and designed the research. TJ, LCGH and TE conducted experiments. SSJ And TJ conducted the analytical work. TJ, LCGH, TE, BB and KPD analysed the data. TJ, LCCH, TE, KPD, BB and SSJ wrote the manuscript. All authors read and approved the manuscript.
Compliance with ethical standards
The study protocol was approved by the Danish Experimental Animal Expectorate (2014-15-0201-00190), and it complies with the NIH guide for care and use of laboratory animals, eighth edition, and was conducted in the animal research facilities at the Department of Experimental Medicine and Institute for Forensic Medicine, both at the Faculty of Health and Medical Sciences, Copenhagen University
Conflict of interest
The authors declare that they have no conflict of interest.
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