Possible markers for postmortem drug redistribution.
The possibility that postmortem biochemical changes in blood might parallel drug redistribution and thus serve as markers was explored in a detailed case study. Eighteen blood and 14 tissue and fluid samples were taken at autopsy 16 h after the death of a 34-year-old female from amitriptyline overdose. Ranges of drug concentrations in blood were amitriptyline 1.8 to 20.2 micrograms/mL, nortriptyline 0.6 to 7.3 micrograms/mL, levels were lowest in femoral vein and highest in pulmonary vein blood. Corresponding levels of 17 amino acids showed markedly different patterns of site-to-site variability. There was a strong positive correlation between individual amino acid and drug concentrations in pulmonary blood samples (n = 5), particularly for glycine, leucine, methionine, serine, and valine. In blood samples from the great veins and right heart (n = 10), the correlation was less strong (r = 0.6 to 0.7). Methionine showed a strong positive correlation in pulmonary samples (r = 0.93), and negative correlation in great veing samples (r = -0.68). Lactic acid showed a strong negative correlation in pulmonary samples (r = -0.93) but a positive correlation in great vein samples (r = 0.71). Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, and bilirubin had a weak positive correlation with drug levels in great vein samples but not pulmonary samples. The results suggest that hepatic enzymes are relatively poor markers for postmortem hepatic drug shifts but that amino acids, particularly methionine, may be useful markers for pulmonary drug shifts.
Langford
A M
AM
University of Dundee, Department of Forensic Medicine, Royal Infirmary, Scotland.
Pounder
D J
DJ
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000097:blood; D000639:Amitriptyline / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D000928:Antidepressive Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000737:chemistry; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000032:analysis; D004386:Duodenum / Q000737:chemistry; D005260:Female; D005554:Forensic Medicine; D006801:Humans; D007583:Jejunum / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008715:Methionine / Q000097:blood; D018482:Muscle, Skeletal / Q000737:chemistry; D009661:Nortriptyline / Q000032:analysis / Q000493:pharmacokinetics / Q000652:urine; D011180:Postmortem Changes; D014018:Tissue Distribution; D014822:Vitreous Body / Q000737:chemistry; D005723:gamma-Glutamyltransferase / Q000097:blood
D000596:Amino Acids; D000928:Antidepressive Agents; D015415:Biomarkers; D001786:Blood Glucose; D000639:Amitriptyline; D008715:Methionine; D009661:Nortriptyline; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin