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