P-糖蛋白抑制剂对紫杉醇大鼠体内药动学的影响

目的:比较和分析3种不同P-糖蛋白(P-glycoprotein,P-gp)抑制剂与紫杉醇注射剂(taxol)联合给予大鼠后,P-gp抑制剂对大鼠体内紫杉醇药动学行为的影响。方法:大鼠分别注射给予taxol或联合给予taxol与环孢素A、维拉帕米、槲皮素,采用HPLC测定大鼠体内紫杉醇血浆药物浓度,以3P97软件求算药动学参数。结果:环孢素A和槲皮素均能使紫杉醇大鼠体内的消除行为减缓与生物利用度提高(P<0.05或P<0.01)。维拉帕米的作用较弱(P>0.05)。结论:由于体内的紫杉醇同时受P-gp和CYP3A酶作用,因此具有P-gp和CYP3A酶双重抑制作用的环孢素A和槲皮素可显著改变紫杉醇体内的药动学行为。

The effect of three different P-glycoprotein inhibitors on the pharmacokinetic behaviors of paclitaxel

OBJECTIVE To compare and analysis the effect of three different P-glycoprotein(P-gp)inhibitors on the pharmacokinetic behaviors of paclitaxel by intravenous administration to rats.METHODS 24 Rats were divided into 4 groups.One group was given Taxol alone and the other three groups were given Taxol with Cyclosporin A(CsA),verapamil or quercetin,respectively.Plasma concentration of paclitaxel was analyzed by HPLC,and pharmacokinetics parameters were calculated by 3P97.RESULTS CsA,verapamil and quercetin decreased the elimination of paclitaxel and increased the AUC of paclitaxel.CONCLUSION Paclitaxel undergoes the elimination effect of P-gp and CYP3A,the agents that simultaneously inhibit P-gp and CYP3A could significantly increase the bioavailability and decrease the elimination of paclitaxel.