Clinical Findings, Elimination Pharmacokinetics, and Tissue Drug Concentrations Following a Fatal Amitriptyline Intoxication

Abstract

Following a serious intoxication with amitriptyline [AMI, an antidepressant], clinical features included deep to moderate coma, respiratory depression, hyperreflexia, sinus tachycardia and a widened QRS interval. Initial plasma levels of AMI and nortriptyline (NOR) were 1070 and 410 ng/ml, respectively. Elimination kinetic measurements indicated a normal plasma half-life of 29.5 h for AMI, and a prolonged elevation of plasma NOR concentrations (about 400 ng/ml) with apparent accumulation. This latter result differed markedly from reported NOR elimination kinetics which have been similar to AMI following low dosage. Postmortem analyses indicated a high degree of tissue binding by both drugs. Various organ concentrations of AMI and NOR ranged to about 15 times the plasma concentrations, while in the central nervous system these ratios approached 35- and 45-fold, respectively. Observation of plasma NOR levels provides a salient indication of the progress of detoxication, and emphasizes the necessity for continued close attention to the maintenance of adequate respiration following massive tricyclic antidepressant overdose when systemic drug levels remained elevated.