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安非他酮过量导致致死性安非他酮(安非他酮缓释片)缓释剂型过量服用时形成药物性胃石:安非他酮及其主要代谢产物的尸检分布情况

Bupropion Overdose Resulted in a Pharmacobezoar in a Fatal Bupropion (Wellbutrin ) Sustained-release Overdose: Postmortem Distribution of Bupropion and its Major Metabolites.

作者信息

Schmit Gregory, De Boosere Evy, Vanhaebost Jessica, Capron Arnaud

机构信息

Department of Pathology, Cliniques Universitaires St Luc, Avenue Hippocrate, 10, 1200, Brussels, Belgium.

Morphology Reasearch Group, Institute for Experimental and Clinical Reasearch, Université Catholique de Louvain, Brussels, Belgium.

出版信息

J Forensic Sci. 2017 Nov;62(6):1674-1676. doi: 10.1111/1556-4029.13497. Epub 2017 Jun 20.

Abstract

Bupropion (BUP) overdose commonly causes generalized seizures and central nervous system depression. The case of a 28-year-old woman who died from a massive lethal overdose with sustained-release bupropion (Wellbutrin 300 mg) is herein presented. The autopsy revealed the presence of a pharmacobezoar consisting of at least 40 tablets in the stomach. Determination of bupropion and its active metabolites (hydroxybupropion, threobupropion, erythrobupropion) was achieved by a liquid chromatographic mass spectrometry (LC-MS/MS) method. Postmortem concentrations for bupropion, hydroxybupropion, threobupropion, and erythrobupropion were obtained in intracranial blood, urine, bile, liver, kidney, and vitreous humor. In this case, intracranial blood level of the parent drug was 1.9 mg/L. Threobupropion was the most abundant metabolite in both blood and urine, 59.3 and 890.6 mg/L. Tissue distribution showed the highest concentration in the liver, 12.3 mg/kg. The 0.8 bupropion concentration ratio vitreous/blood suggested that vitreous could be a valuable specimen for toxicological analysis should postmortem blood be unavailable.

摘要

安非他酮(BUP)过量通常会导致全身性癫痫发作和中枢神经系统抑制。本文介绍了一名28岁女性因服用大量缓释安非他酮(安非他酮300毫克)致死过量的病例。尸检发现胃内存在一个由至少40片药片组成的药物性胃石。采用液相色谱-质谱联用(LC-MS/MS)法测定安非他酮及其活性代谢物(羟基安非他酮、苏式安非他酮、赤式安非他酮)。在颅内血、尿、胆汁、肝、肾和玻璃体液中获得了安非他酮、羟基安非他酮、苏式安非他酮和赤式安非他酮的死后浓度。在该病例中,母体药物的颅内血药浓度为1.9毫克/升。苏式安非他酮是血液和尿液中含量最高的代谢物,分别为59.3毫克/升和890.6毫克/升。组织分布显示肝脏中的浓度最高,为12.3毫克/千克体重。玻璃体液与血液的安非他酮浓度比为0.8,这表明在死后无法获得血液的情况下,玻璃体液可能是毒理学分析的一个有价值的样本。

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