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在体外研究中,药物在牙本质中的沉积取决于药物浓度、接触时间以及药物的物理化学性质。

In vitro studies on the dependence of drug deposition in dentin on drug concentration, contact time, and the physicochemical properties of the drugs.

机构信息

Institute of Forensic Medicine, Forensic Toxicology, Medical Center-University of Freiburg, Freiburg, Germany.

Faculty of Medicine, University of Freiburg, Freiburg, Germany.

出版信息

Arch Toxicol. 2023 Oct;97(10):2675-2685. doi: 10.1007/s00204-023-03573-6. Epub 2023 Aug 16.

Abstract

The chemical analysis of dental hard tissues can provide information on previous drug use due to the deposition of drugs into this tissue. For the interpretation of analytical results in, e.g., postmortem toxicology or regarding archeological samples, the influence of drug dosing, consumption frequency, duration of intake and type of drug on analyte concentrations in teeth has to be characterized. To approximate these correlations, in vitro models were applied to investigate the time dependency of drug deposition via and against pulp pressure (perfusion studies) and the concentration dependency of drug deposition via oral cavity (incubation study) as well as the influence of de- and remineralization (pH cycling) on the incorporation of drugs in bovine dentin pellets. Some of the drugs of abuse most relevant in forensic case work (amphetamines, opiates, cocaine and benzoylecgonine) were applied. Concentrations in dentin samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after pulverization and extraction via ultrasonication with methanol. The studies showed that drug deposition in dentin likely depends on the physicochemical properties of the drug molecules as well as on the duration of contact with drugs via the blood stream and on drug concentrations present in the oral cavity. Higher drug concentrations in teeth can result from a more frequent or longer drug use. In addition, intake of higher doses or oral/inhalative consumption can also be expected to lead to higher drug concentrations. These findings can be helpful for the interpretation of postmortem cases.

摘要

牙体硬组织的化学分析可以提供有关先前药物使用的信息,因为药物会沉积在这种组织中。为了解释例如法医毒理学或考古样本中的分析结果,必须描述药物剂量、消耗频率、摄入持续时间和药物类型对牙齿中分析物浓度的影响。为了近似这些相关性,应用体外模型来通过和对抗牙髓压力(灌注研究)研究药物沉积的时间依赖性,以及通过口腔(孵育研究)研究药物沉积的浓度依赖性,以及去矿化和再矿化(pH 循环)对药物在牛牙本质丸中的掺入的影响。应用了一些在法医案例工作中最相关的滥用药物(安非他命、阿片类药物、可卡因和苯甲酰可待因)。通过与甲醇的超声粉碎和提取,在牙本质样品中分析了浓度。研究表明,牙本质中的药物沉积可能取决于药物分子的物理化学性质,以及通过血流与药物接触的持续时间以及口腔中存在的药物浓度。牙齿中更高的药物浓度可能是由于更频繁或更长时间的药物使用。此外,预计更高的剂量摄入或口服/吸入消费也会导致更高的药物浓度。这些发现有助于解释死后案例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e58b/10474980/130c0fd82e45/204_2023_3573_Fig1_HTML.jpg

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