急性中毒
ENGLISH ABSTRACT
活性炭对喹硫平吸附效果的体外和大鼠体内评价方法研究
巴根
曹德才
石齐芳
谢未然
张孛妍
孙昊
毛征生
张劲松
作者及单位信息
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DOI: 10.3760/cma.j.issn.1671-0282.2025.03.009
Study on in vitro and in rat’s vivo evaluation methods of quetiapine adsorption by activated charcoal
Ba Gen
Cao Decai
Shi Qifang
Xie Weiran
Zhang Beiyan
Sun Hao
Mao Zhengsheng
Zhang Jinsong
Authors Info & Affiliations
Ba Gen
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Cao Decai
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 117004, China
Shi Qifang
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Xie Weiran
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Forensic Medicine, Nanjing Medical University, Nanjing 210029, China
Zhang Beiyan
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Sun Hao
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Emergency, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China
The Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing 210029, China
Mao Zhengsheng
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Forensic Medicine, Nanjing Medical University, Nanjing 210029, China
Zhang Jinsong
Institute of Poisoning, Nanjing Medical University, Nanjing 210029, China
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
The Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing 210029, China
·
DOI: 10.3760/cma.j.issn.1671-0282.2025.03.009
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摘要

目的探明活性炭在不同条件下对喹硫平吸附的影响,构建活性炭对喹硫平吸附效果的评价方法,评价活性炭在体外和体内对喹硫平吸附效果。

方法体外实验通过活性炭在不同有机溶剂含量、有机溶剂类型、吸附温度、吸附时间以及pH值等条件与喹硫平共孵育,平衡、离心后取上清,用LC-MS/MS检测上清中喹硫平的浓度,计算吸附率。以Log10活性炭浓度作为自变量,活性炭对喹硫平的吸附率为因变量,通过Origin 2021软件进行函数拟合。体内实验大鼠经灌胃给予喹硫平后,实验组灌胃给予125 mg/mL的活性炭,给药前、给药后0.17 h, 0.33 h, 0.50 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, 24 h眼眶采血,血浆样本前处理后用LC-MS/MS检测喹硫平的浓度,通过DAS 2.0软件计算对照组及实验组中喹硫平的药代动力学参数。

结果有机溶剂含量、吸附温度、吸附时间以及pH值等因素影响活性炭对喹硫平的清除效果,最终优化选择统一的体外吸附实验方法。拟合了100个不同的吸附函数模型,筛选出Boltzmann函数是活性炭对喹硫平的最优吸附函数模型。药代动力学结果显示,与对照组相比,给予活性炭的实验组喹硫平C max和AUC显著降低。

结论:体外与体内实验结果表明,活性炭在体外与体内均对喹硫平具有一定的吸附效果。

活性炭;急性中毒;喹硫平;药代动力学;函数模型
ABSTRACT

ObjectiveTo investigate the impact of various conditions on the adsorption of quetiapine by activated carbon, establish a method for evaluating the adsorption efficacy of activated carbon on quetiapine, and assess the adsorption effects both in vitro and in vivo.

MethodsIn vitro experiments involved incubating activated carbon with quetiapine under different conditions, including varying organic solvent contents, types of organic solvents, adsorption temperatures, adsorption times, and pH. After reaching equilibrium, the mixtures were centrifuged, and the supernatants were collected. The concentration of quetiapine in the supernatants was measured using LC-MS/MS, and the adsorption rates were calculated. The log-transformed concentration of activated carbon was used as the independent variable and the adsorption rate as the dependent variable for function fitting using Origin 2021 software. In the in vivo experiments, rats were administered quetiapine orally, followed by 125 mg/mL of activated carbon in the experimental group. Blood samples were collected at multiple time points pre- and post-administration (0.17 h, 0.33 h, 0.50 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h). Plasma samples were pre-treated and the quetiapine concentrations were determined using LC-MS/MS. Pharmacokinetic parameters for both control and experimental groups were calculated using DAS 2.0 software.

ResultsThe factors such as organic solvent content, type of organic solvent, adsorption temperature, adsorption time, and pH value significantly influenced the adsorption efficiency of quetiapine by activated carbon, leading to the optimization and standardization of the in vitro adsorption methodology. Among the 100 different adsorption function models tested, the Boltzmann function was identified as the most suitable models for describing the adsorption of quetiapine by activated carbon. Pharmacokinetic analysis showed that the experimental group treated with activated carbon exhibited significantly reduced C max and AUC for quetiapine compared to the control group.

ConclusionThe results of both in vitro and in vivo experiments demonstrate that activated carbon effectively adsorbs quetiapine, providing a potential method for mitigating quetiapine absorption.

Activated charcoal;Acute poisoning;Quetiapine;Pharmacokinetics;Functional modeling
Zhang Jinsong, Email: nc.defudabe.umjnosjgnahz;
Mao Zhengsheng, Email: nc.defudabe.umjngnehsgnehzoam
引用本文

巴根,曹德才,石齐芳,等. 活性炭对喹硫平吸附效果的体外和大鼠体内评价方法研究[J]. 中华急诊医学杂志,2025,34(03):335-341.

DOI:10.3760/cma.j.issn.1671-0282.2025.03.009

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活性炭作为毒物清除吸附剂已有百年历史,国内外报道了大量有关活性炭在毒物清除中的应用研究 [ 1 , 2 , 3 ],其中体外实验证明活性炭可以吸附有机磷农药 [ 4 ]、亚硝酸钠 [ 5 ]和γ-羟基丁酸 [ 6 ]等药(毒)物。然而,既往由于国内医用活性炭的缺乏,在临床上没有得到广泛的应用,临床医务人员对其使用方法、疗效和不良反应等了解有限。相反,国外有临床研究表明活性炭在体内可以吸附清除对乙酰氨基酚 [ 7 ]、玛伐凯泰 [ 8 ]和卡马西平 [ 9 ]等药(毒)物。近年来,随着国外活性炭产品进入国内市场,以及国内厂家产品逐步应用于临床,使活性炭在临床应用与推广成为可能,2016年《急性中毒诊断与治疗中国专家共识》 [ 10 ]建议对于短时间内摄入了有潜在毒性、过量的药物或毒物的患者,可通过口服活性炭进行毒物清除。2018年度美国毒物控制中心协会基于毒物数据系统报告显示抗精神类药物是第二大类致成人中毒药物 [ 11 ],喹硫平是其中普遍应用的药物之一,活性炭对于此类药物中毒的救治效果尚不明确,而且活性炭在国内其他急性中毒救治中的实际应用仍然有限,限制活性炭应用的主要原因包括活性炭对毒物清除效果的评价没有统一标准 [ 12 , 13 ]、活性炭对不同毒物的吸附选择性仍不明确以及活性炭在体内对毒物的清除效果缺少相关报道 [ 14 ]等。本研究探讨了活性炭在不同条件下对喹硫平的吸附能力,建立了体外和体内的标准评价方法。
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备注信息
A
张劲松,Email: nc.defudabe.umjnosjgnahz
B
毛征生,Email: nc.defudabe.umjngnehsgnehzoam
C

巴根:论文撰写、实验操作;曹德才、石齐芳、张孛妍:数据收集、整理和分析;谢未然:样本处理;毛征生:提供研究经费、研究设计、论文修改;张劲松、孙昊:文章指导

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所有作者声明无利益冲突
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中华预防医学会中毒控制科研项目 (CPMZAD2024005)
上海市法医学重点实验室资助项目 (KF202205)
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