Postmortem redistribution and degradation of dothiepin. Corrigendum to the timedependant postmortem redistribution of antipsychotic drugs forensic sci. Post mortem redistribution of drugs following death there can be rapid changes in cellular biochemistry as autolysis proceeds, and drugs and other poisons may be released from their binding sites in tissues and major organs. The post mortem redistribution of a number of psychiatric drugs was investigated. To consider the role of the physicochemical properties of drugs in their postmortem redistribution, we designed the present study to investigate the influence of lipophilicity using an experimental rabbit model.
Resultsdrugs that have a high postmortem central to peripheral ratio. Detailed human case data is presented to illustrate the dramatic extent of the phenomenon of post mortem drug redistribution. Estimating antemortem drug concentrations from postmortem. At nida, shewas the lead associate investigator in a study evaluating the. It is thought that all drugs will be affected to some extent by postmortem redistribution and the main contributing factors are 1 the time between death and sampling, 2 the sites of sampling. Identification of a postmortem redistribution factor f. Identification of a postmortem redistribution factor f for. A portion of liver, the gastric contents and blood collected from heart and femoral sites was obtained from cases and analyzed by liquid chromatographymass spectrometry. Postmortem redistribution of fentanyl in the rabbit blood.
During the postmortem interval, drugs from the gastrointestinal tract, lungs, heart, or liver may travel via diffusion through blood vessels or via direct diffusion into other organs or vessels. Pounder dj, jones gr 1990 postmortem drug redistributiona toxicological nightmare. An animal model of postmortem amitriptyline redistribution. Postmortem redistribution of fentanyl in blood american. The postmortem to antemortem ratio was compared with the postmortem central to peripheral ratio, using cardiac blood as a central site and femoral blood as a peripheral site. The redistribution of selected psychiatric drugs in post. Postmortem redistribution pmr is a phenomenon in postmortem toxicology that has been recognized for over two decades.
Sedimentation of blood after death may also affect the drug blood concentration obtained. Mechanisms underlying postmortem redistribution of drugs. Postmortem redistribution pmr refers to the changes that may occur in drug. The data suggests that there is a post mortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with resultant artefactual elevation of drug levels in blood. Tolerance is also discussed as an aid to interpreting results from a habitualchronic user of medications andor drugs of abuse. Drug levels are altered after death by diffusion of the substances throughout the body postmortem redistribution and certain substances are produced or degraded in the postmortem period. The analysis involved 50 commonly used drugs and their concentrations in.
Detailed human case data is presented to illustrate the dramatic extent of the phenomenon of postmortem drug redistribution. Jun 22, 2017 it is thought that all drugs will be affected to some extent by postmortem redistribution and the main contributing factors are 1 the time between death and sampling, 2 the sites of sampling. The mechanisms that cause these phenomena are complex and often intricate. Nevertheless, reasonable assessments can still be made by the pathologist and toxicologist as to the contribution that commonlyabused drugs may have made to the death. Identification of a postmortem redistribution factor f for forensic toxicology iain m mcintyre 0 0 forensic toxicology laboratory manager, county of san diego medical examiners office, 5570 overland ave. After death, they are redistributed to the surrounding tissues. Quantitative post mortem analysis one of the central tenets of clinical pharmacology is that the pharmacological action of a drug is determined by its concentration at the site of action.
Postmortem redistribution, in which drug concentrations in blood specimens from various areas of the body change during the postmortem interval, has been observed for many drugs. It involves the redistribution of drugs into blood from solid. Mar 12, 2014 postmortem redistribution pmr refers to the changes that may occur in drug concentrations after death. Femoral blood was collected from 273 cases at admission to mortuary ad and at postmortem pm. To help avoid common pitfalls, the text demonstrates the proper interpretation of postmortem drug levels based on knowledge of pharmacokinetics, metabolism, and pharmacogenetics.
Consequently, postmortem concentrations in blood may not always replicate the antemortem drug levels. Mechanisms involved in postmortem redistribution are both complicated and poorly understood. Micro redistribution acidification passive diffusion blood coagulation and hypostasis postmortem circulation putrefaction micro redistribution enzymes, proteases, phosphatases, glucosidases all leak into the cytoplasm further breaking down cellular components macromolecules, proteins, and the drugs. Drug diffusion from the gut and other reservoirs must be differentiated from diffusion from sites of high drug concentrations such as heart, lung, and liver. However, postmortem drug concentrations in blood do follow some generally accepted. Postmortem toxicology of commonlyabused drugs alexander r allan ian s d roberts abstract postmortem redistribution and other changes present major obstacles to the interpretation of drug concentrations in the dead. A study of drug use, pathology and postmortem tissue. The data suggests that there is a postmortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with.
They also cast uncertainty on the interpretation of drugs where analogous studies are incomplete or totally absent. Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50. The timedependant postmortem redistribution of antipsychotic drugs. The term postmortem redistribution was used by koren and macleod in the title for their 1985 paper on changes in digoxin concentration after death, based on experiments in the rat. Drug concentrations obtained from post mortem samples do not necessarily reflect the concentrations at the time of death, and variations of concentration may be observed between different sites andor different sampling times. Postmortem redistribution and other changes present major obstacles to the interpretation of drug concentrations in the dead. Identification of a postmortem redistribution factor f for forensic toxicology, journal of analytical science and technology, 2014, pp. Postmortem redistribution type of collection tubes and storage conditions. Expert witness deposition explains postmortem distribution of. Furthermore, as both methamphetamine and amphetamine have previously been shown to have liverperipheral.
Pdf mechanisms underlying postmortem redistribution of drugs. It involves the redistribution of drugs into blood from solid organs such as the lungs, liver, a. Whether pmr occurs in any given case is dependent on characteristics of the individual. These data show that postmortem redistribution occurs for both methamphetamine and amphetamine, revealing that postmortem blood concentrations are. The data suggests that there is a postmortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with resultant artefactual elevation of drug levels in blood.
Pdf postmortem drug concentrations do not necessarily reflect concentrations at the time of death, as drug levels may vary according to the. Postmortem redistribution pmr is an important factor to consider in forensic toxicology. Postmortem drug redistributiona toxicological nightmare. The rate and extent of this movement varies according to several factors, including the nature of the drug and the time interval between death and postmortem specimen collection. This reference also provides explanation of the complicating conditions for the interpretation of the toxicological results due to postmortem decomposition, embalming artifacts and the postmortem redistribution of drugs. View pdf download pdf postmortem drug concentrations in blood may not always reflect antemortem drug concentrations in blood due to the movement of the. The data suggests that there is a postmortem diffusion of drugs along a concentration gradient, from sites of high concentration in solid organs, into the blood with resultant artefactual. Interpreting postmortem drug analysis and redistribution. They administered radioiodinelabelled digoxin to rats 2 h before death. Multiple interacting factors alter the measured concentration of almost all drugs after death. Postmortem redistribution pmr refers to the changes that may occur in drug concentrations after death. Postmortem drug concentrations in blood may not always reflect antemortem drug concentrations in blood due to the movement of the drugs after death. These studies provide certain clarification to drug level interpretation.
Literature supports the model describing drugs with a liver l concentration to peripheral blood p concentration ratio less than 5 lkg being prone to. This is believed to occur largely through diffusion from a high to a low concentration and is believed to be time dependent. Postmortem clinical pharmacology europe pmc article. The most significant aspect is the phenomenon of postmortem redistribution. Postmortem toxicology of abused drugs considers the role of toxicology in the investigation of homicide, suicide, accident, natural death, and overdose. Jul 12, 2009 so if postmortem redistribution has a role in the case, and we will use the number here, if mr. Pounder dj, jones gr 1990 post mortem drug redistribution a toxicological nightmare. During the past 15 years, much work has been performed using human case information and animal studies to illustrate and validate the phenomena of postmortem drug redistribution. Postmortem drug redistribution omics international. The analysis involved 50 commonly used drugs and their concentrations in femoral blood, other blood such as.
The best assessments may be obtained by the implementation of the investigation along the following. Pdf the timedependant postmortem redistribution of. One of the most difficult responsibilities of the forensic toxicologist is the interpretation of postmortem drug levels and their possible significance as to behavior andor cause of death. These phenomena, collectively termed post mortem redistribution, concern numerous molecules medications, drugs of abuse, gases, etc. Identification of a postmortem redistribution factor f for forensic. The timedependant post mortem redistribution of antipsychotic drugs. Consequently,compilations oflethal concentrationsare misleading. Iain m mcintyre and christina meyer escottpostmortem drug redistribution. Pdf postmortem drug redistribution semantic scholar. Pmr is a process whereby drugs can diffuse from contiguous tissues with higher drug concentrations into the surrounding blood, and the concentration of drugs at certain anatomic sites usually cardiac or central blood can. Pdf on dec 1, 2011, brigitte desharnais and others published postmortem redistribution of drugs. The phenomenon is referred to as postmortem redistribution pmr. Drugs detected included five selective serotonin reuptake inhibitors.
The processes of postmortem redistribution result in the migration of drugs between blood and tissues. However, post mortem redistribution is still not completely understood. Within the torso, the major organs constitute potential drug. Interpreting postmortem drug analysis and redistribution in. The effect of the postmortem interval on the redistribution of drugs. Several studies have tried to investigate post mortem redistribution including how drugs diffuse in the body after death. Post mortem toxicology of commonlyabused drugs alexander r allan ian s d roberts abstract post mortem redistribution and other changes present major obstacles to the interpretation of drug concentrations in the dead. These are considered in the area of drug redistribution from sites of high tissue concentrations. Many drugs are sequestered antemortem in organs qualified as drug reservoirs table i. The postmortem redistribution of a number of psychiatric drugs was investigated. Site to site variability of postmortem drug concentrations in liver and lung.
In the postmortem setting evaluating drug concentrations presents an additional challenge due to factors such as postmortem redistribution of drugs 6, 7, bacterial metabolism 8 and the post. To consider the role of the physicochemical properties of drugs in their post mortem redistribution, we designed the present study to investigate the influence of lipophilicity using an experimental rabbit model. Postmortem available for download and read online in other formats. Literature supports the model describing drugs with a liver l concentration to peripheral blood p concentration ratio less than 5 lkg being prone to little or no pmr. Postmortem drug redistribution a toxicological nightmare. Interpreting postmortem drug analysis and redistribution in determining cause of death. Fentanyl showed marked redistribution into the femoral and pulmonary veins of the rabbit through 48 hours after the. Methamphetaminea study of postmortem redistribution. The concentrations of many drugs are affected by postmortem redistribution through the vascular system from the major organs, by direct postmortem diffusion from organ to organ, and sometimes by incomplete distribution. This redistribution may coexist with redistribution from the gastrointestinal tract, and it could be very difficult to determine the main mechanism when drugs were taken orally. Pelisseralicott al, gaulier jm, champsaur p, marquet p.
Jan 15, 2009 post mortem redistribution and other changes present major obstacles to the interpretation of drug concentrations in the dead. Methamphetaminea study of postmortem redistribution, journal of analytical toxicology, volume 23, issue 1, 1 january 1. Postmortem drug concentrations do not necessarily reflect concentrations at the time of death, as drug levels may vary according to the sampling site and the interval between death and specimen collection. The effect of the postmortem interval on the redistribution. The best assessments may be obtained by the implementation of.