50 Years of postmortem redistribution research: What have we learned?

Interpretation of postmortem (PM) drug concentrations is challenging as these concentrations do not necessarily reflect drug concentrations at the time of death, due to PM changes in drug concentrations primarily caused by PM redistribution (PMR). In this review article, we discuss the advantages and limitations of different study designs historically utilized to investigate PMR and their most important findings. PM administration studies in cadavers suggest time dependent redistribution by diffusion from a single high concentration reservoir to surrounding fluids and tissues. In animal studies PMR within the first hours PM was observed. Cardiac blood is prone to early PM concentration increases, likely as a result of PMR along large blood vessels from drug reservoirs in the lung tissue. This is potentially aided by rapid PM acidification of blood. An increasing postmortem interval (PMI) is associated with advanced decomposition of the body facilitating diffusion of drugs. Environmental factors influence both the rate of decomposition and the rate of PM diffusion. Human studies investigating PMR of drugs are challenging due to the inherit limitations associated with the lack of control over variables such as drug dose, post dose survival time and PMI. The most useful data regarding PMR in human PM cases is provided by larger studies that performed sampling at multiple time points PM. An alternative is comparing antemortem (AM) and PM drug concentrations. Lastly, distribution of a drug at a single PM timepoint can be compared between drugs with different physicochemical properties and/or between different subgroups of the study population.