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大鼠口服山奈酚与乙醇相互作用的药代动力学评价

Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats.

作者信息

Zhou Zhaoxiang, Wang Meng, Guo Zengjun, Zhang Xiaoying

出版信息

Acta Pharm. 2016 Dec 1;66(4):563-568. doi: 10.1515/acph-2016-0044.

Abstract

This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

摘要

本研究旨在探究乙醇对大鼠中槲皮素口服生物利用度的影响,即揭示它们之间可能的相互作用。将槲皮素(100或250 mg kg-1体重)通过灌胃给予大鼠,同时给予或不给予乙醇(600 mg kg-1体重)。静脉注射(10和25 mg kg-1体重)槲皮素用于测定生物利用度。血浆中槲皮素的浓度通过超高效液相色谱法进行估算。在共同给药期间,观察到血浆浓度-时间曲线下面积以及峰浓度显著增加,同时全身清除率急剧下降。因此,口服对照组中槲皮素的生物利用度分别为3.1%(100 mg kg-1体重)和2.1%(250 mg kg-1体重)。在乙醇共同给药期间,前者增加了4.3%,后者增加了2.8%。细胞膜通透性增加以及乙醇与槲皮素在细胞色素P450酶上的相互作用可能会提高大鼠中槲皮素的口服生物利用度。

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