Abstract
Reversing ventricular ectopy with plasma alkalinization followng acute tricyclic antidepressant overdose is a recognized mode of therapy. The mechanism responsible for this effect is unclear. Changes in plasma protein binding of free drug, effects of the sodium ion on the myocardium, and alterations of plasma concentrations of alpha-1 acid glycoprotein may all interact to alter toxicity of tricyclics in overdose. An in vitro investigation using equilibrium dialysis was designed to examine the effect of altering plasma pH on percentage of free amitriptyline at clinical overdose plasma concentrations. A 1973 report on this effect lacked adequate controls and was faulty in experimental protocol. The current investigation used plasma concentrations typically present in amitriptyline overdose, a sensitive gas liquid chromatographic assay to detect total and free drug, and adequate control of plasma pH. The results of two separate experiments demonstrated a significant decrease in percentage of free amitriptyline of 20% over a pH range of 7.0–7.4 ( P < 0.05) and 42% over a pH range of 7.4–7.8 ( P < 0.05). The rate of change in slope in both experiments was not significantly different ( P < 0.01) indicating similar effects of pH change on plasma protein binding of amitriphyline within the two groups.
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