POSTMORTEM RELEASE OF AMITRIPTYLINE FROM THE LUNGS - A MECHANISM OF POSTMORTEM DRUG REDISTRIBUTION

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 t he inferior vena cava, and tissue samples from the lungs, heart, liver , right kidney, thigh muscle, the wail of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A signi ficant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem th e concentration increase was 4.4 +/- 0.5-fold (P < 0.0 1) and 3.0 +/- 1.1-fold (P < 0.05) as compared to the antemortem values observed in h eart blood and blood from the inferior vena cava, respectively (mean /- SEM). In the lungs there was a fall in the concentration of AMI fro m 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8 mumol/kg at 96 h post mortem (P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart mus cle and liver an increase in drug concentration was observed. In anima ls where the lungs were removed agonally (n = 7), the drug concentrati on in heart blood had increased significantly less at 2 h postmortem. Accordingly, this animal model demonstrates that postmortem drug relea se from the lungs play an important role in the phenomenon of postmort em drug redistribution.