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December 14, 1994

The Toxicity and Dose of Desipramine Hydrochloride-Reply

Author Affiliations

The New York State Psychiatric Institute Columbia University College of Physicians and Surgeons New York, NY

JAMA. 1994;272(22):1720-1721. doi:10.1001/jama.1994.03520220013007

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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