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In vivo pharmacokinetics, distribution, and excretion of an anticancer agent isolated from red ginseng, in rat.
Xenobiotica ( IF 1.8 ) Pub Date : 2020-05-14 , DOI: 10.1080/00498254.2020.1765265
Qian Zheng 1, 2, 3 , Ruili Wang 1, 2 , Nanqi Zhang 3, 4 , Cuizhu Wang 3 , Pingya Li 3
Affiliation  

  1. The compound 20(S),25-epoxydammarane-3β,12β,24α-triol (24-hydroxy-panaxadiol or 24-OH-PD), isolated from the red Panax ginseng CA Meyer possesses anticancer activity. Our aim was to study the pharmacokinetic characteristics of 24-OH-PD, which is essential for pre-clinical research during the development of new drugs.

  2. In this study, a simple and sensitive ultra-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was established and used for studying the pharmacokinetics, in vitro protein binding, tissue distribution, and elimination profiles of 24-OH-PD in rats.

  3. 24-OH-PD was characterized by linear pharmacokinetics in the dose range of 2.5–10 mg/kg and had relatively longer half-life (4.82–5.45 h) than the other ginsenosides. It had a wide tissue distribution profile in rats and was primarily distributed in the lung. Within 96 h of intravenous administration, 13.84% of 24-OH-PD was excreted out via feces and 0.02% via urine in its unchanged form.

  4. In conclusion, a simple LC-MS/MS method with high sensitivity and selectivity was established for the quantification of 24-OH-PD.



中文翻译:

从红参中分离出的抗癌药在大鼠体内的体内药代动力学,分布和排泄。

  1. 从红色人参CA Meyer分离出的化合物20(S),25-环氧丹玛烷3β,12β,24α-三醇(24-羟基-人参二醇或24-OH-PD)具有抗癌活性。我们的目的是研究24-OH-PD的药代动力学特性,这对于新药开发期间的临床前研究至关重要。

  2. 在这项研究中,建立了一种简单而灵敏的超高效液相色谱-质谱(LC-MS / MS)方法,并用于研究24-OH-PD的药代动力学,体外蛋白质结合,组织分布和消除特征在大鼠中。

  3. 24-OH-PD的线性药代动力学特征是剂量范围为2.5–10 mg / kg,并且比其他人参皂苷具有相对更长的半衰期(4.82–5.45 h)。它在大鼠中具有广泛的组织分布特征,并且主要分布在肺中。在静脉内给药的96小时内,有13.84%的24-OH-PD通过粪便排泄,而0.02%的尿液以不变的形式排泄。

  4. 总之,建立了一种具有高灵敏度和选择性的简单LC-MS / MS方法,用于定量24-OH-PD。

更新日期:2020-05-14
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