Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 17, Changlexi Street, Xi'an 710032, Shaanxi, China.
Biomed Pharmacother. 2012 Mar;66(2):98-102. doi: 10.1016/j.biopha.2011.11.012. Epub 2011 Dec 30.
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.
法乐紫杉醇（SHR110008）目前正在进行 I 期临床试验，是一种具有强大抗肿瘤作用的新型紫杉烷类药物。本研究旨在评估法乐紫杉醇在大鼠体内的药代动力学特征和血浆蛋白结合情况。数据来自几项临床前研究，其中评估了单次静脉注射（5mg/kg）后法乐紫杉醇在大鼠体内的药代动力学、组织分布和排泄情况。采用 LC-MS/MS 法测定法乐紫杉醇的浓度。采用非房室模型分析血浆浓度-时间数据。采用超滤法评估血浆蛋白结合情况。法乐紫杉醇的药代动力学特征与之前在大鼠中的数据相似。法乐紫杉醇迅速分布到正常组织，除脑外，各组织中的药物浓度均为血浆中的 2-8 倍，但半衰期和平均停留时间相似。肾脏是暴露量最大的主要排泄器官，可能负责法乐紫杉醇的消除。约 0.21%和 0.72%的法乐紫杉醇在 24 小时内通过尿液和粪便排泄，0.25%的法乐紫杉醇在单次给药后 12 小时内通过胆汁排泄。法乐紫杉醇在浓度为 100-5000ng/mL 的血浆中与蛋白结合的能力几乎呈线性。本研究首次提供了法乐紫杉醇的完全吸收、分布和排泄特征，这将有助于其临床方案设计。
