Tricyclic Antidepressants: Interpretation of Blood and Tissue Levels in Fatal Overdose

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Abstract
Tricyclic antidepressant concentrations were measured in the blood, liver, and myocardium of 29 decedents with fatal tricyclic overdose. Eighty-three percent of the cases involved either amitriptyline (14 cases) or doxepin (10 cases). Concentrations of each parent drug and its respective N-desmethyl metabolite when available were compared within the various tissues. The mean concentration of parent drug in liver was significantly higher than that in myocardium which, in turn, was significantly higher than that in blood (p < 0.01). Furthermore, the three series of levels correlated with each other. The mean ratio of parent drug level to metabolite level (P/M) in blood was significantly lower (p < 0.01) in the present series of fatal overdoses (1.43) than in a previously reported series of nonfatal tricyclic overdoses (4.62). Both the mean L/B (ratio of parent drug level in liver to that in blood) and the mean M'/B (ratio of parent drug level in myocardium to that in blood) were appreciably higher than the corresponding mean ratios in fatal overdose involving seven other drugs (p < 0.01). In fatal amitriptyline overdose the mean P/M ratios did not differ significantly between blood, liver, or myocardium and showed statistical correlation with one another in these three tissues.