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The in vivo pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its in vitro intestinal absorption study using UPLC-MS/MS.
Xenobiotica ( IF 1.3 ) Pub Date : 2017-12-27 , DOI: 10.1080/00498254.2017.1416206
Xiuxiu Liu 1 , Minghai Tang 2 , Taohong Liu 1 , Chunyan Wang 2 , Qiaoxin Tang 2 , Yaxin Xiao 1 , Ruixin Yang 1 , Ruobing Chao 1
Affiliation  

1. Mesaconine, an ingredient from Aconitum carmichaelii Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the in vivo process and intestinal absorptive behavior of mesaconine should be investigated comprehensively.

2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the in vivo pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using in vitro everted rat gut sac model.

3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat’s intestine is a first-order process with the passive diffusion mechanism.



中文翻译:

使用UPLC-MS / MS进行大鼠美沙康宁的体内药代动力学,组织分布和排泄研究以及体外肠道吸收研究。

1. Mesaconine,从配料附子Debx,已被证明有强心作用。为了进一步发展和更好地阐明药理,应全面研究美沙康宁的体内过程和肠道吸收行为。

2.建立了超高效液相色谱-串联质谱(UPLC-MS / MS)方法,并验证了大鼠血浆,组织匀浆,尿液和粪便中美沙康宁的定量含量,以研究体内药代动力学特征,组织分布和排泄物。使用体外翻出的大鼠肠囊模型研究了mesaconine的肠道吸收行为。

3. Mesaconine在组织中分布良好,在粪便中发现大量未改变的形式。口服后很难吸收到血液循环系统中。mesaconine口服生物利用度不足可能主要归因于其缺乏亲脂性,因此肠道通透性低。褪黑素在大鼠肠中的吸收是具有被动扩散机制的一级过程。

更新日期:2017-12-27
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