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Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical
Matej Dobravc Verbič1,2, Iztok Grabnar2, Florian Eyer3
1Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
Abstract:
Over the past decade, quetiapine has become one of the most commonly used psychotropic drugs in acute intoxication events worldwide. A structured literature review and analysis were conducted to assess the relationship between the kinetic and dynamic profiles in acute quetiapine intoxication. The correlation between dose and peak serum concentration (cmax) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and cmax as predictors of the most common clinical events, signs and symptoms. One hundred and thirty-four cases of acute quetiapine ingestion were included in the analysis, with a median ingested dose of 10 g and a median cmax of 4 mg/L. The typical half-life was estimated to be 16.5 h, significantly longer than at therapeutic doses. For the immediate-release formulation, a biphasic disposition could not be excluded. Dose and cmax demonstrated a weak but significant correlation (r = 0.256; N = 63; p = 0.043). Central nervous system depression and tachycardia were the most common clinical signs. Higher doses and concentrations increased the risk of severe intoxication and were good predictors of intubation, tachycardia, hypotension, QTc prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and cmax that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or cmax > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.
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