Matej Dobravc Verbič, Iztok Grabnar, Florian Eyer, Miran Brvar
{"title":"急性喹硫平中毒:摄入剂量、血清浓度和临床表现之间的关系--结构化文献回顾与分析。","authors":"Matej Dobravc Verbič, Iztok Grabnar, Florian Eyer, Miran Brvar","doi":"10.3390/jox14040085","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>max</sub>) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and c<sub>max</sub> 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<sub>max</sub> 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<sub>max</sub> demonstrated a weak but significant correlation (r = 0.256; N = 63; <i>p</i> = 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<sub>c</sub> prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and c<sub>max</sub> that increased the risk for individual signs and symptoms varied widely. However, doses > 3 g or c<sub>max</sub> > 2 mg/L can be considered as alert levels that represent a high risk for severe clinical course of acute quetiapine intoxication.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"14 4","pages":"1570-1594"},"PeriodicalIF":6.8000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503392/pdf/","citationCount":"0","resultStr":"{\"title\":\"Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical Presentation-Structured Literature Review and Analysis.\",\"authors\":\"Matej Dobravc Verbič, Iztok Grabnar, Florian Eyer, Miran Brvar\",\"doi\":\"10.3390/jox14040085\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sub>max</sub>) was determined using Pearson's correlation coefficient. Binary logistic regression was used to evaluate dose and c<sub>max</sub> 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<sub>max</sub> 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<sub>max</sub> demonstrated a weak but significant correlation (r = 0.256; N = 63; <i>p</i> = 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<sub>c</sub> prolongation and seizures, but not QRS prolongation, arrhythmia, heart block, hypokalaemia or acidosis. The thresholds for dose and c<sub>max</sub> that increased the risk for individual signs and symptoms varied widely. 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Acute Quetiapine Intoxication: Relationship Between Ingested Dose, Serum Concentration and Clinical Presentation-Structured Literature Review and Analysis.
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.
期刊介绍:
The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (“stranger to life”) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; pathophysiological interactions of natural and synthetic chemicals; development of biochemical indicators including new “-omics” approaches to identify biomarkers of exposure or effects for xenobiotics.