Postmortem redistribution of two antipsychotic drugs, haloperidol and thioridazine, in the rat.
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.
Castaing
Nadege
N
CHU de Bordeaux, Laboratoire de Pharmacologie Clinique et Toxicologie, F-33076 Bordeaux, France.
Titier
Karine
K
Canal-Raffin
Mireille
M
Moore
Nicholas
N
Molimard
Mathieu
M
D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005554:Forensic Medicine; D006220:Haloperidol / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D023421:Models, Animal; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar; D013881:Thioridazine / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D006220:Haloperidol; D013881:Thioridazine