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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 30, Issue 7, September 2006,
pp.419-425
Postmortem Redistribution of Two Antipsychotic Drugs, Haloperidol
and Thioridazine, in the Rat
Nadege Castaing, Karine Titier, Mireille Canal-Raffin, Nicholas Moore,
and Mathieu Molimard
CHU de Bordeaux, Laboratoire de Pharmacologie Clinique et Toxicologie, F-33076
Bordeaux, France and Université Victor Segalen, Département de
Pharmacologie, F-33076 Bordeaux, France
Antipsychotic drugs may be associated with arrhythmia, ventricular
fibrillation, or torsades de pointes, which can result in sudden death. These
drugs could therefore be found in postmortem toxicological analyses of autopsy
specimens following unexplained sudden death. The drug concentrations in tissues
and body fluids change between the death and postmortem specimens collection
because of postmortem redistribution. For this reason, it is often difficult
to interpret the postmortem analysis. The aim of this study was to investigate
postmortem redistribution of the two cardiotoxic antipsychotic drugs, haloperidol
and thioridazine, in order to interpret the postmortem analysis. We have chosen
the rat as an animal model. The rats received 1 mg/kg of haloperidol and 5 mg/kg
of thioridazine by intraperitoneal injection. They were sacrificed and left
at room temperature for 2, 6, 12, 24, or 48 h, at which times blood and tissue
samples were taken. The drug analyses in tissues and blood were done using a
liquid chromatography– tandem mass spectrometry method. Our results show
that there is a redistribution of the two drugs from the lung to the cardiac
blood. The concentration of the antipsychotic drugs in the lung decreased rapidly,
whereas in the cardiac blood, this concentration increased within the first
2 h postmortem. By 48 h after death, the concentrations of the antipsychotic
drugs were about twice as high as the initial concentrations in the cardiac
blood. For the lungs, a decrease of 50% was observed between 0 and 48 h. Only
myocardium and muscle concentrations did not change with the postmortem delay.
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