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目的评价Labrasol作用下对紫杉醇经小肠吸收的影响。方法0.5mg紫杉醇和0.5mg Labrasol装入明胶胶囊中,并以羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)包裹胶囊,观察胶囊的体外释药性能。在乙醚麻醉下通过聚乙烯管给大鼠口服5粒胶囊,对照组口服同剂量的不含Labrasol的胶囊。于给定的时间间隔取血,用HPLC测定大鼠血液中的药物浓度。另同法制备含0.1mg荧光素钠和0.5mg Labrasol明胶胶囊和不含Labrasol的荧光素钠明胶胶囊,分别给大鼠口服5粒胶囊。用HPLC测定血药浓度。用WinNolin软件计算血药浓度曲线下面积。结果制备的肠溶性紫杉醇胶囊在人工胃液中2h无药物释放,而在人工肠液中4h内累积释药量几乎达到100%。大鼠口服肠溶性紫杉醇明胶胶囊时,大鼠血浆浓度-时间曲线下面积(AUC)为(582.43±181.99)μg.h.L-1,而在Labrasol作用下,AUC增加到(1379.43±487.29)μg.h.L-1,具有统计学意义(P<0.05),表明在Labrasol的作用下,将有更多的紫杉醇吸收到血液中。但同剂量的Labrasol对荧光素钠的吸收没有促进作用。结论Labrasol可能通过抑制小肠黏膜的P-糖蛋白而促进紫杉醇经小肠的吸收。
Objective To evaluate the effect of Labrasol on the intestinal absorption of paclitaxel. Methods 0.5 mg paclitaxel and 0.5 mg Labrasol were loaded into gelatin capsules. The capsules were encapsulated with hydroxypropyl methylcellulose phthalate (HPMCP) to observe the in vitro drug release properties. Five capsules were orally administered to rats through polyethylene tubing under ether anesthesia, while the control group was orally dosed with the same dose of capsules containing no Labrasol. Blood was drawn at a given time interval and the drug concentration in rat blood was determined by HPLC. The same method with the preparation of 0.1mg sodium fluorescein and 0.5mg Labrasol gelatin capsules and Labrasol-free sodium fluorescein gelatin capsules, rats were orally 5 capsules. Plasma concentration was determined by HPLC. Use WinNolin software to calculate the area under the plasma concentration curve. Results The preparation of enteric-coated paclitaxel capsule had no drug release in artificial gastric juice for 2 hours, but accumulated in artificial intestinal juice almost reached 100% in 4 hours. The oral administration of enteric-coated paclitaxel gelatin capsules in rats resulted in an area under the curve of plasma concentration-time (AUC) of (582.43 ± 181.99) μg.hL-1, while the AUC increased to (1379.43 ± 487.29) μg with Labrasol. hL-1, statistically significant (P <0.05), indicating that more paclitaxel will be absorbed into the blood with Labrasol. However, the same dose of Labrasol did not promote the absorption of sodium fluorescein. Conclusion Labrasol may promote the absorption of paclitaxel through the small intestine by inhibiting the P-glycoprotein of small intestinal mucosa.