Key Concepts in Postmortem Drug Redistribution

Abstract

Postmortem redistribution (PMR) refers to the changes that occur in drug concentrations after death. It involves the redistribution of drugs into blood from solid organs such as the lungs, liver, and myocardium. Drug properties such as volume of distribution, lipophilicity, and pKa are important factors. Basic, highly lipophilic drugs with a volume of distribution greater than 3 l/kg are most likely to undergo PMR. Examples include the tricyclic antidepressants, digoxin, and the amphetamines. The anatomical location of blood sampling can influence the drug concentration. The ideal site is a ligated or clamped femoral vein. Medical toxicologists participating in forensic cases involving drugs likely to undergo PMR must be aware of its potential contribution to the postmortem drug concentration. Correlation with laboratory data and any available antemortem or perimortem clinical information is necessary to render an appropriate opinion on the cause of death.

Sorption of amitriptyline and amphetamine to mixed-mode solid-phase microextraction in different test conditions

“…Postmortem, blood pH drops from 7.4 to around 5.5 due to an accumulation of acidic glucose metabolites [26]. The ionic composition of blood changes as Na + concentration decreases and K + concentration increases due to failure of the Na + /K + /ATPase pump [27]. Furthermore, the C18/SCX fiber was exposed to mixtures of amphetamine and amitriptyline to study potential competition effects on sorption affinities within mixtures.…”

Prevalence of adverse drug combinations in a large post-mortem toxicology database

“…Verapamil increases the digoxin concentration by inhibition of P-glycoprotein mediated excretion [37]. Digoxin is known to undergo post-mortem re-distribution leading to difficulty in interpretation of post-mortem digoxin concentrations [38]; however, in this study, results exclusively from peripheral blood samples were included. Only one case was identified in which the digoxin concentration was high enough to meet the set criteria of a potential ADI and to reach a suggested level of life-threatening toxicity [39].…”

The influence of putrefaction and sample storage on post-mortem toxicology results

“…This is a phenomenon that has been known for quite some time, and there are many articles and reviews available on this topic [4,6,18,25]. Drugs that are prone to redistribution also have a high volume of distribution, as these are sequestered in cellular materials, and upon cell death and autolysis are released [4]; redistribution is also dependent on the protein binding tendency and lipophilicity of the drug [26], along with the position of the body and any subsequent movement prior to autopsy [4].…”

“…This is a phenomenon that has been known for quite some time, and there are many articles and reviews available on this topic [4,6,18,25]. Drugs that are prone to redistribution also have a high volume of distribution, as these are sequestered in cellular materials, and upon cell death and autolysis are released [4]; redistribution is also dependent on the protein binding tendency and lipophilicity of the drug [26], along with the position of the body and any subsequent movement prior to autopsy [4]. This phenomenon occurs when drugs that are present in relatively high concentration in the stomach, intestines or other organs diffuse into the surrounding tissues, blood and other bodily fluids such as cerebrospinal fluid or vitreous humor [18], and is also known to occur in central sites such as with heart blood [27].…”

“…Enzymes are also released during autolysis and therefore cause breakdown of cellular materials, which can result in exogenous compounds being released from cellular materials [4]. Bacteria present within the body are also capable of using some particular drugs and/or metabolites as substrates, thereby creating a pathway for concentration changes during the post-mortem interval [5].…”