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植物药代动力学:卡马西平和拉莫三嗪及其相互作用。

Pharmacokinetics in Plants: Carbamazepine and Its Interactions with Lamotrigine.

机构信息

Department of Soil and Water Sciences, The Robert H. Smith Faculty of Agriculture, Food and Environment , The Hebrew University of Jerusalem , P.O. Box 12, Rehovot 7610001 , Israel.

The Hebrew University Center of Excellence in Agriculture and Environmental Health , P.O. Box 12, Rehovot 7610001 , Israel.

出版信息

Environ Sci Technol. 2018 Jun 19;52(12):6957-6964. doi: 10.1021/acs.est.8b01682. Epub 2018 May 31.

Abstract

Carbamazepine and lamotrigine prescribed antiepileptic drugs are highly persistent in the environment and were detected in crops irrigated with reclaimed wastewater. This study reports pharmacokinetics of the two drugs and their metabolites in cucumber plants under hydroponic culture, testing their uptake, translocation, and transformation over 96 h in single and bisolute systems at varying pH. Ruling out root adsorption and transformations in the nutrient solution, we demonstrate that carbamazepine root uptake is largely affected by the concentration gradient across the membrane. Unlike carbamazepine, lamotrigine is adsorbed to the root and undergoes ion trapping in root cells thus its translocation to the shoots is limited. On the basis of that, carbamazepine uptake was not affected by the presence of lamotrigine, while lamotrigine uptake was enhanced in the presence of carbamazepine. Transformation of carbamazepine in the roots was slightly reduced in the presence of lamotrigine. Carbamazepine metabolism was far more pronounced in the shoots than in the roots, indicating that most of the metabolism occurs in the leaves, probably due to higher concentration and longer residence time. This study indicates that the uptake of small nonionic pharmaceuticals is passive and governed by diffusion across the root membrane.

摘要

卡马西平和拉莫三嗪是两种常用于治疗癫痫的处方药物,它们在环境中具有高度持久性,并已在使用再生废水灌溉的农作物中被检测到。本研究报告了这两种药物及其代谢物在水培条件下黄瓜植株中的药代动力学,在单一和双溶液体系中,在不同 pH 值条件下,测试了它们在 96 小时内的吸收、转运和转化情况。通过排除根系对营养溶液的吸附和转化,我们证明卡马西平的根系吸收主要受到跨膜浓度梯度的影响。与卡马西平不同,拉莫三嗪被根系吸附,并在根细胞中发生离子捕获,因此其向地上部分的转运受到限制。基于此,卡马西平的吸收不受拉莫三嗪的影响,而拉莫三嗪的吸收在卡马西平存在的情况下增强。拉莫三嗪在根系中的转化在卡马西平存在的情况下略有减少。卡马西平在地上部分(叶片)的代谢比在根系中的代谢更为显著,这表明大部分代谢发生在叶片中,可能是由于叶片中浓度更高且停留时间更长。本研究表明,小的非离子型药物的吸收是被动的,由跨根膜的扩散控制。

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