Following amitriptyline or imipramine overdose by 30 patients, total
plasma concentrations ranged from 29 to 1732 ng/ml but did not correlate
well with physical findings or most electrocardiographic changes. Only
those patients with a QRS interval greater than 0.1 second had
significantly elevated plasma levels. However, a plasma level ratio of the
parent drug (amitriptyline, imipramine) to its respective N-desmethyl
metabolite (nortriptyline, desmethylimipramine) greater than or equal to
2.0 was associated with an acute overdose. This ratio was more useful than
total plasma levels in differentiating an overdose from a therapeutic dose
with associated toxicity and an elevated steady-state plasma level.
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