The Toxicity and Dose of Desipramine Hydrochloride-Reply

J. John Mann, MD
JAMA. 1994;272(22):1720-1721. doi:10.1001/jama.1994.03520220013007.
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In Reply.  —Drs Amitai and Frischer agree with our report that desipramine is more lethal on overdose than other tricyclics. Amitai et al1 found that the in vitro RBC/plasma ratio of desipramine (1.60) was no different from nortriptyline (1.57) or nordoxepin (1.62); parent compounds had lower ratios (eg, 0.73 for imipramine and 0.45 for amitriptyline). In vivo, their results1 in cases of drug overdose are consistent and suggest that the parent compound washes out of RBCs and plasma faster than the desmethyl metabolite, and that the parent compound, more so than the metabolite, is found in higher concentrations in the plasma than the RBCs. However, the presence of coma was unrelated to plasma or RBC concentrations of parent drug or metabolite. The duration of the QRS interval correlated with RBC and plasma levels of metabolite, but not parent compound. Therefore, these results do not demonstrate that the RBC/plasma


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