马拉硫磷在大鼠和人体内的体外代谢清除率。

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-05-17 DOI:10.1016/j.tiv.2025.106080

Gopinath Nallani , Appavu Chandrasekaran , Kelem Kassahun , Li Shen , Rick Reiss , Paul Whatling

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引用次数: 0

摘要

测定了成年、幼年大鼠和人肝微粒体对马拉硫磷的体外内在清除率。由于消除速度快，没有检测到母体的水平，马拉硫磷的清除率是通过其代谢物：马拉硫磷单羧酸（MMCA）和马拉硫磷的形成动力学计算的。为了将体外数据与体内暴露相关联，对成年大鼠进行了单次静脉注射（10 mg/kg bw）或口服剂量（150 mg/kg bw）后的药代动力学（PK）研究。体外动力学数据表明，马拉硫磷在成人和幼年人肝微粒体（HLM）中通过MMCA形成的代谢清除率相同，但在成年大鼠肝微粒体（RLM）中，其清除率比幼年高约10倍。两种和年龄组间malaoxon的形成率差异在3.5倍以内。表征了丙二醇的形成动力学

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In vitro metabolic clearance of malathion in rats and humans

In vitro intrinsic clearance of malathion was determined in adult and juvenile rat and human liver microsomes. Due to rapid elimination with no detectable levels of the parent, clearance rates of malathion were calculated from formation kinetics of its metabolites: malathion monocarboxylic acid (MMCA) and malaoxon. To correlate in vitro data to in vivo exposure, pharmacokinetics (PK) study was performed in adult rats following a single i.v. (10 mg/kg bw) or oral dose (150 mg/kg bw). The in vitro kinetics data indicate that the metabolic clearance of malathion via formation of MMCA was at the same rate in adult and juvenile human liver microsomes (HLM), but in rat liver microsomes (RLM) the rate was about 10-fold higher in adults compared to juveniles. The rate of formation of malaoxon among the two species and age groups was within 3.5-fold difference. The formation kinetics of malaoxon represented <0.5 % of that observed for MMCA in both rats and humans. As seen in the in vitro results, following i.v. or oral dosing in rats, malathion was not detectable with MMCA being the major metabolite. The kinetics data from this study were useful for the development of a PBPK model for malathion.

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.