To the Editor: In cases of sudden unexpected death, toxicological studies are performed as part of an autopsy to help establish causality. Toxic postmortem drug concentrations can lead to erroneous conclusions with resulting liability claims, insurance denials, and significant emotional turmoil for all involved. However, postmortem drug concentrations may not accurately reflect antemortem drug levels. Postmortem redistribution of a drug may be the basis for elevated or toxic drug concentrations after death (1). Postmortem drug concentrations vary greatly from drug to drug because of differences in the volume of distribution, the elimination half-life, the site of the postmortem blood sample, protein binding, and the amount of time elapsed between death and obtaining of the postmortem blood sample. To our knowledge, this is the first reported case of postmortem redistribution of clozapine.

We believe that this is a case of postmortem redistribution of clozapine. Postmortem redistribution of tricyclic antidepressants has been described in the literature (1). Clozapine is similar to tricyclic antidepressants in chemical structure, volume of distribution (6 liter/kg), and protein binding (97% protein bound), leading one to anticipate similar redistribution effects. The time elapsed was sufficient (>2 hours) (2), and central blood samples are associated with higher postmortem concentrations (3).

Clinicians should be aware of the possibility of postmortem redistribution of clozapine because the implications can be significant. More reporting of such cases is needed to establish the phenomenon. Instances in which antemortem plasma levels were obtained and in which there is no possibility of overdose would be most useful.