鸦胆子油乳对大鼠体内紫杉醇药代动力学的影响

Effect of Brucea Javanica Oil Emulsion on the Pharmacokinetics of Paclitaxel in Rats in Vivo

目的探讨鸦胆子油乳对大鼠体内紫杉醇药代动力学的影响。方法将16只SD大鼠随机分为紫杉醇联用鸦胆子油乳组(PTX+BJOE组)和紫杉醇组(PTX组),各8只。PTX+BJOE组大鼠腹腔注射鸦胆子油乳注射液2.7 mL/kg,PTX组大鼠腹腔注射等量生理盐水,连续5 d,最后1 d给药30 min后,两组大鼠均腹腔注射紫杉醇注射液3.5 mL/kg;给药后0,0.083,0.5,1,2,4,8,24,48 h时经大鼠眼眶静脉采血,并分离血浆。采用超高效液相色谱-质谱法测定大鼠血浆中紫杉醇的浓度,采用GraphPad Prism 7.04软件绘制血药浓度-时间曲线,使用DAS 2.0软件计算药代动力学参数。结果与PTX组比较,PTX+BJOE组大鼠给药后0.5,4,8,24 h时紫杉醇的血药浓度均显著升高(P<0.05);PTX+BJOE组大鼠血浆中0-∞时血药浓度-时间曲线下面积(AUC_(0-∞))显著升高(P<0.05),半衰期(t_(1/2))显著缩短(P<0.05);达峰浓度(C_(max))升高,表观分布容积(Vd)降低,但均无显著差异(P>0.05)。结论鸦胆子油乳联用紫杉醇可能存在相互作用,鸦胆子油乳可能会使紫杉醇的血药浓度增大、药效增强,临床联用时可能需减小紫杉醇的剂量。

Objective To investigate the effect of Brucea Javanica Oil Emulsion(BJOE)on the pharmacokinetics of paclitaxel(PTX)in vivo.Methods Sixteen SD rats were randomly divided into the PTX+BJOE group and the PTX group,with eight rats in each group.The rats in the PTX+BJOE group were intraperitoneally injected with 2.7 mL/kg of BJOE Injection.The rats in the PTX group were intraperitoneally injected with an equal amount of physiological saline for 5 d.After 30 min of administration on the last day,the rats in the two groups were intraperitoneally injected with 3.5 mL/kg of PTX Injection.Blood was collected from the orbital vein of rats at 0,0.083,0.5,1,2,4,8,24,and 48 h after administration,and plasma was separated.The concentration of paclitaxel in rat plasma was determined by the ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS)method.The plasma concentration-time curve was drawn by the GraphPad Prism 7.04 software,and the pharmacokinetic parameters were calculated by the DAS 2.0 software.Results Compared with those in the PTX group,the blood concentration of paclitaxel significantly increased at 0.5,4,8,and 24 h after administration in the PTX+BJOE group(P<0.05);the area under the plasma concentration-time curve at 0-∞(AUC_(0-∞))significantly increased(P<0.05),and the half-life(t_(1/2))of PTX significantly shortened in the PTX+BJOE group(P<0.05);the peak concentration(C_(max))increased,while the apparent distribution volume(Vd)decreased in the PTX+BJOE group,but there was no significant difference(P>0.05).Conclusion There may be drug-drug interaction between BJOE and PTX.BJOE may increase the blood concentration and enhance the efficacy of PTX,and it may be necessary to reduce the dosage of PTX when the clinical combination is performed.