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Pharmacokinetics and tissue distribution in rats of a novel anticancer platinum compound LLC-1903.
Xenobiotica ( IF 1.902 ) Pub Date : 2020-02-19 , DOI: 10.1080/00498254.2020.1728421
Yingxue Li,Fanzhuo Meng,Zhijian Chen,Fuguo Han,Donglin He,Yanli Hao,Anli Gao,Jing Jiang,Zhao Wang,Weiping Liu,Qingfei Liu

LLC-1903, a novel anticancer compound, was synthesized by optimizing the structure, which was derived from altering the leaving group of lobaplatin. It has an excellent in vitro anti-cancer activity, high water solubility, high stability in solution and low in vivo toxicity according to our former study. The plasma pharmacokinetics (PK) and tissue distribution of LLC-1903 and lobaplatin in rats were determined after intravenous administration of a single dose (0.06 mmol/kg body weight). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of platinum (Pt) in plasma and tissue samples. Most PK parameters of the Pt in LLC-1903 showed a significant difference from those of lobaplatin. The plasma level of LLC-1903 is only half of that of lobaplatin (p < 0.01) which could be the direct result of faster drug clearance. The tissue distribution showed that both LLC-1903 and lobaplatin were mainly found in the liver and kidney, and less in other organs. At four time points (0.083, 0.5, 1 and 4 h) after administration, the tissue concentrations of LLC-1903 were almost always significantly higher than those of lobaplatin (p < 0.05 or p < 0.01).
更新日期:2020-02-19

 

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