Post‐mortem clinical pharmacology

Abstract

Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post-mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post-mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post-mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post-mortem redistribution. Consequently, compilations of 'lethal concentrations' are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post-mortem measurements.

Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

“…For many substances there is no sharp dividing line between toxic and lethal drug concentrations [25]. When a drug exists as a racemic mixture the picture is even more complicated [26][27][28].…”

Comparative Study of Blood Metal Levels in Post-Mortem and Living Population Samples from Dammam, KSA

“…However, Postmortem changes, such as post-mortem diffusion and redistribution, make the interpretation of xenobiotic concentrations measured in post-mortem samples difficult or impossible. Moreover, postmortem xenobiotic concentrations unpredictably change with the site and time of sampling, as a result of the phenomenon of postmortem redistribution [16][17][18][19][20]. The phenomenon of post-mortem redistribution was coined by Pounder and Jones [21].…”

Complete Republication: National Association of Medical Examiners Position Paper: Recommendations for the Investigation, Diagnosis, and Certification of Deaths Related to Opioid Drugs

“…Tolerance accounts for some of the overlap between therapeutic, supratherapeutic, and lethal concentrations of opioid analgesics observed in decedents, complicating the interpretation of postmortem concentrations of opioids and other drugs [22]. There is no reliable quantifiable measure of drug tolerance before or after death.…”