Dobravc Verbič Matej, Grabnar Iztok, Eyer Florian, Brvar Miran
Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
The Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
J Xenobiot. 2024 Oct 18;14(4):1570-1594. doi: 10.3390/jox14040085.
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 (c) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and c 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 c 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 c demonstrated a weak but significant correlation (r = 0.256; N = 63; = 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, QT prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and c that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or c > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.
在过去十年中，喹硫平已成为全球急性中毒事件中最常用的精神药物之一。进行了一项结构化文献综述和分析，以评估急性喹硫平中毒时动力学和动态特征之间的关系。使用Pearson相关系数确定剂量与血清峰值浓度（c）之间的相关性。二元逻辑回归用于评估剂量和c作为最常见临床事件、体征和症状的预测指标。134例急性喹硫平摄入病例纳入分析，摄入剂量中位数为10g，c中位数为4mg/L。典型半衰期估计为16.5小时，明显长于治疗剂量时的半衰期。对于速释制剂，不能排除双相处置。剂量和c显示出弱但显著的相关性（r = 0.256；N = 63；P = 0.043）。中枢神经系统抑制和心动过速是最常见的临床体征。较高的剂量和浓度增加了严重中毒的风险，是插管、心动过速、低血压、QT延长和癫痫发作的良好预测指标，但不是QRS延长、心律失常、心脏传导阻滞、低钾血症或酸中毒的预测指标。增加个体体征和症状风险的剂量和c阈值差异很大。然而，剂量>3g或c>2mg/L可被视为警戒水平，代表急性喹硫平中毒严重临床过程的高风险。
