Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution

Abstract

An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A significant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem the concentration increase was 4.4 +/- 0.5-fold (P < 0.01) and 3.0 +/- 1.1-fold (P < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean +/- SEM). In the lungs there was a fall in the concentration of AMI from 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8 mumol/kg at 96 h postmortem (P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart muscle and liver an increase in drug concentration was observed. In animals where the lungs were removed agonally (n = 7), the drug concentration in heart blood had increased significantly less at 2 h postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)