Serum Diazepam Concentrations in Overdose: Their Significance

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Abstract
Total serum benzodiazepine concentrations were correlated with clinical manifestations in 93 cases of diazepam overdose. Diazepam and nordiazepam were also each separately determined in 101 serum specimens from cases of diazepam overdose, including 27 cases from the aforementioned clinical correlation study. In addition, serum nordiazepam concentrations were measured in five cases of clorazepate overdose. Concentrations of total benzodiazepine ranged from 1 to 22 μg/ml. All patients survived with supportive therapy only. Each of the 25 patients who had ingested only diazepam was awake or in grade 0 coma, even when drug concentrations were ten-fold greater than the accepted upper limit of the therapeutic range. None of the patients who had ingested only diazepam needed hospitalization; all were discharged from acute medical care after a period of emergency room observation. The ratios of parent drug to N-desmethyl metabolite (nordiazepam) in those overdose specimens analyzed by gas chromatography averaged 3:1. This high ratio may be useful in differentiating acute overdose from high concentrations resulting from chronic therapy. Although determination of diazepam concentrations aid in establishing that an overdose has occurred, when more than grade I or II coma is present, other drugs or an alternative explanation should be sought, regardless of the drug concentration.