河北医科大学学报 ›› 2025, Vol. 46 ›› Issue (8): 933-938.doi: 10.3969/j.issn.1007-3205.2025.08.011

• • 上一篇    下一篇

不同神经激肽1受体拮抗剂对大鼠体内白蛋白结合型紫杉醇药动学的影响

  

  1. 1.河北医科大学第二医院药学部，河北 石家庄 050073；2.河北医科大学药学院，河北 石家庄 050017

  • 出版日期:2025-08-25 发布日期:2025-08-29
  • 作者简介:秦源蔓（2000-），女，河北秦皇岛人，河北医科大学第二医院理学硕士研究生，从事药物体内相互作用相关研究。

  • 基金资助:
    河北省医学科学研究课题计划（20221145）

Effects of different neurokinin-1 receptor antagonists on the pharmacokinetics of albumin-bound paclitaxel in rats

  1. 1.Department of Pharmacy, the Second Hospital of Hebei Medical University, Shijiazhuang 
    050073, China; 2.School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China

  • Online:2025-08-25 Published:2025-08-29

HTML

PDF (PC)

4

摘要： 目的 探讨不同神经激肽1受体拮抗剂（阿瑞匹坦、奈妥匹坦）对大鼠体内白蛋白结合型紫杉醇药动学的影响。
方法 将32只SD大鼠随机分为4组（n=8），分别灌胃给予生理盐水、阿瑞匹坦（arepitant,APT）混悬液、奈妥匹坦帕洛诺司琼复方制剂（netupitant/palonosetron,NEPA）混悬液、盐酸帕洛诺司琼（palonosetron,PALO）混悬液，1 h后四组大鼠均给予顺序尾静脉注射白蛋白紫杉醇和顺铂（platinum-based chemotherapy regimen,TP）化疗方案，给药后眼眦取血，测定大鼠血浆中紫杉醇的浓度，对比各组药动学参数差异。
结果 和TP组相比，联用阿瑞匹坦后（TP组vs. TP+APT组）大鼠血浆中紫杉醇的血浆浓度-时间曲线下面积（area under theconcentration-time curve,AUC）AUC0-t、AUC0-∞分别增加了25.78%（P=0.005）、24.92%（P=0.006），表观分布容积（apparent volume of distribution,Vd）、清除率（clearance,CL）分别下降29.25%（P=0.001）、21.19%（P=0.003），差异有统计学意义；联用奈妥匹坦帕洛诺司琼组（TP组vs. TP+NEPA组）后大鼠血浆中紫杉醇的最高血药浓度（maximum plasma concentration,Cmax）、AUC0-t、AUC0-∞分别增加28.33%（P＜0.001）、42.46%（P＜0.001）、40.26%（P＜0.001），Vd、CL分别下降35.40%（P＜0.001）、29.85%（P＜0.001），差异有统计学意义；联用帕洛诺司琼（TP组vs. TP+PALO组）后大鼠血浆中紫杉醇的Vd下降19.57%（P=0.016），差异有统计学意义，其他药动学参数差异无统计学意义。
结论 PALO对白蛋白结合型紫杉醇的药动学无明显影响，阿瑞匹坦及奈妥匹坦均会增加白蛋白结合型紫杉醇在大鼠体内的暴露量，且奈妥匹坦对白蛋白结合型紫杉醇体内暴露量的影响更大，因此临床联用阿瑞匹坦或奈妥匹坦时应注意监测白蛋白紫杉醇的血药浓度。


关键词: 白蛋白结合型紫杉醇, 受体, 神经激肽1, 药物相互作用

Abstract: Objective To investigate the effects of different neurokinin-1 receptor antagonists ［aprepitant (APT), netupitant］ on the pharmacokinetics of albumin-bound paclitaxel in rats. 
Methods Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups (n=8), and then gavaged with normal saline, APT suspension, netupitant/palonosetron (NEPA) compound preparation suspension, and palonosetron (PALO) suspension, respectively. One hour afterwards, taxol and platinum-based chemotherapy regimen (TP) was sequentially given to therats in the four groups. Albumin-bound paclitaxel and cisplatin were sequentially injected into the tail vein of the rats in the four groups. After administration, blood was taken from the canthus of the eyes. The concentration of paclitaxel in the plasma of the rats was determined, and the differences of pharmacokinetic parameters in each group were compared. 
Results Compared with the TP group, the area under the plasma concentration-time curve (AUC), namely AUC0-t and AUC0 -∞, of paclitaxel in the plasma of rats treated with APT (TP group vs. TP+APT group) increased by 25.78% (P=0.005) and 24.92% (P=0.006), respectively, while apparent volume of distribution (Vd) and clearance(CL) decreased by 29.25% (P=0.001) and 21.19% (P=0.003), respectively, with statistical differences. The maximum plasma concentration (Cmax), AUC0-t, AUC0-∞ of paclitaxel in plasma of rats in the combination treatment group (TP group vs. TP + NEPA group) increased by 28.33% (P＜0.001), 42.46% (P＜0.001), 40.26% (P＜0.001), respectively， while Vd and CL decreased by 35.40% (P＜0.001), and 29.85% (P＜0.001), respectively, with statistical differences. The Vd of paclitaxel in rat plasma decreased by 19.57% (P=0.016) after combined use of PALO (TP group vs. TP+PALO group), with statistical difference, and other pharmacokinetic parameters had no statistical difference. 
Conclusion PALO has no significant effect on the pharmacokinetics of albumin-bound paclitaxel, while APT and netupitant can increase the exposure of albumin-bound paclitaxel in rats, and netupitant has a greater effect on the exposure of albumin-bound paclitaxel in rats.Therefore, in clinical practice, attention should be paid to monitoring the blood concentration of albumin-bound paclitaxel when it is used in combination with APT or netupitant.


Key words: albumin-bound paclitaxel, receptors, neurokinin-1, drug interactions

版权所有 © 《河北医科大学学报》编辑部
本系统由北京玛格泰克科技发展有限公司设计开发