Journal Published Online: 01 January 1993
Volume 38, Issue 1

An Animal Model of Postmortem Amitriptyline Redistribution

CODEN: JFSCAS

Abstract

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood—PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 ± 0.8 (mean ± sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 ± 0.3 (n = 5), and at 96 h 55.1 ± 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.

Author Information

Hilberg, T
National Institute of Forensic Toxicology, Oslo, Norway
Bugge, A
National Institute of Forensic Toxicology, Oslo, Norway
Beylich, K-M
National Institute of Forensic Toxicology, Oslo, Norway
Ingum, J
National Institute of Forensic Toxicology, Oslo, Norway
Bjørneboe, A
National Institute of Forensic Toxicology, Oslo, Norway
Mørland, J
National Institute of Forensic Toxicology, Oslo, Norway
Pages: 10
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Stock #: JFS13378J
ISSN: 0022-1198
DOI: 10.1520/JFS13378J