京大戟对紫杉醇口服生物利用度的影响

摘要

Objective To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co- administered orally. Methods Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively. Results In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63%in radix euphorbiae pekinensis group. The average AB%in verapamil group was about 1.5 times that of the blank group. Conclusion Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.%目的：评价合用京大戟提取物对紫杉醇经大鼠不同肠段透过性和口服生物利用度的影响。方法分别采用体外Ussing Chamber实验和大鼠in vivo实验，选用P-糖蛋白（P-gp）抑制剂维拉帕米为阳性对照，对比京大戟提取物对紫杉醇经不同肠段透过的差异性和口服生物利用度评价。紫杉醇的体外透过液和血药浓度分别用HPLC方法和LC-MS/MS方法进行测定。结果Ussing Chamber实验中，京大戟组紫杉醇经空肠、回肠粘膜透过时，吸收方向转运（M-S）和分泌方向转运（S-M）与阳性对照组和空白组比较，表观渗透系数（Papp）均有显著性差异（P<0.05），但在结肠S-M组与空白组相比没有显著性差异（P>0.05）。表明京大戟提取物能提高紫杉醇经肠粘膜的透过性，其作用主要发生在空肠、回肠段。大鼠in vivo实验结果显示，合用京大戟提取物后，紫杉醇的药时曲线下面积（AUC）和最高血浆浓度（Cmax）的平均值显著大于空白组，明显大于阳性对照组。京大戟组紫杉醇的绝对生物利用度（AB%）为7.63%，是空白对照组的2.7倍，阳性对照组的1.8倍。结论合用京大戟提取物，能显著提高紫杉醇经肠道的吸收，在一定程度上能促进紫杉醇的口服生物利用度。