Preclinical pharmacokinetic analysis of felotaxel (SHR110008), a novel derivative of docetaxel, in rats and its protein binding ability in vitro

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• 作者：Yi Ding ; WenXing Liu ; ChengTao Lu ; Jing Yang ; YanRong Zhu ; Ying Song ; ZhongYing Ma ; Lin Yang ; YanYan Jia ; ^{jiayanyan-2004@hotmail.com} ; AiDong Wen ; ^{adwen-2004@hotmail.com}
• 关键词：Pharmacokinetics ; Felotaxel ; SHR110008 ; Rats ; Taxane
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：2012
• 期刊代码：36_07533322
• 类别：med
• 出版时间：March, 2012
• 卷：66
• 期：2
• 页码：98-102
• 文件大小：365 K

摘要

Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new taxane with potent antitumor effects. The purpose of this research was to evaluate the pharmacokinetic profiles of felotaxel in rats and the protein binding in plasma. Data were collated from several preclinical investigations, where the plasma pharmacokinetics, tissue distribution and excretion of felotaxel were assessed after a single intravenous (i.v.) injection (5 mg/kg) to rats. Samples felotaxel concentration was determined by a LC-MS/MS method. The plasma concentration versus time data was analyzed non-compartmental model. Plasma protein binding was assessed using ultrafiltration. Pharmacokinetic properties of felotaxel were similar to the previous data from the rats. Felotaxel was rapidly distributed to normal tissues, drug concentrations in the tissues tested except the brain were two to eight times higher than those in plasma, but half-lives and mean residence times were similar. The kidneys manifested as the dominant organs with high exposure that might be responsible for elimination of felotaxel. Approximately 0.21%and 0.72%of felotaxel was excreted via the urine and feces within 24 h; 0.25%was excreted into the bile up to 12 h after a single dose. The protein binding ability of felotaxel with concentration 100-5000 ng/mL in the plasma was nearly linear. This study first provided the full absorption, distribution, and excretion characteristics of felotaxel, which would be helpful for its clinical regiment design.