Possible Markers for Postmortem Drug Redistribution

Abstract

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 μg/mL, nortriptyline 0.6 to 7.3 μg/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, γ-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.

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

“…On the other hand, the drug level in pericardial fluid, as was illustrated by the example of amitriptyline and nortryptyline, was not much increased. It was up to 2.5 times higher for amitriptyline (in comparison with the drug level in the femoral vein) and in one case even lower for nortryptyline [19,23,36].…”

“…Indeed, the postmortem toxicological data bore that out; the heart of the deceased contained about a 7 times higher concentration than the femoral vein [127]. The extensive tissue distribution of TCAs is in accordance with their high lipophilicity and the large volume of distribution [20,23]. Accumulation of TCAs in the heart was also confirmed by the mean Kp values for amitriptyline (4.6), nortriptyline (7.3), doxepin (3.7), desipramine (4.6) and imipramine (4.3) [8].…”

Evaluation of postmortem redistribution phenomena for commonly encountered drugs

“…PMR is one of many factors that may lead to changes in drug concentrations after death. It was first reported by Gee et al [1] and many studies have been performed to prove the occurrence of this phenomenon [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. It was reported that drug concentrations in the body may change according to the time of death, environment, sampling site, volume of distribution, diffusion, redistribution in body cavities and drug metabolism after death [19].…”

Post-mortem toxicology: A pilot study to evaluate the use of a Bayesian network to assess the likelihood of fatality

“…Preliminary work in the late 1990s suggested that five amino acids (methionine, leucine, valine, glycine and serine) showed strong positive correlation to drug concentrations of the tricyclic antidepressant amitriptyline (known to undergo extensive redistribution due to its high volume of distribution) analysed in post-mortem pulmonary blood samples. The results suggested that the amino acids, in particular methionine, may be a suitable marker for redistribution artefact for pulmonary drug shifts 13 . As of yet, a marker for this phenomenon has not been elucidated.…”

“…It has now been established and has become common practice, that peripheral blood should be obtained from a femoral vessel 4,12 , yet it remains that the extent of redistribution artefacts is an unknown quantity. Whilst markers for the extent of redistribution have been evaluated 13 it still remains a challenging factor in the interpretation of post-mortem toxicology. Similarly the published reference data has evolved from that reported in serum samples to include whole blood 14 as well as distinguishing from data derived from a single drug to that in combination with alcohol and/or other drugs.…”