冰片对甲氨蝶呤透过血脑屏障影响的实验研究

Experimental study on the effect of borneol for methotrexate penetrating across blood brain barrier

目的研究冰片对甲氨蝶呤(抗肿瘤药)透过血脑屏障的影响。方法12只日本大耳白兔随机分为试验组和对照组,试验组给予冰片0.7 g.kg-1(75%乙醇溶解)灌胃;对照组以75%乙醇灌胃1 h后,2组均耳缘静脉注射甲氨蝶呤100 mg.kg-1;用高效液相色谱法测定不同时间点血液和脑脊液的甲氨蝶呤浓度,用3P97软件计算药代动力学参数。结果试验组、对照组在脑脊液药代动力学参数:Cm ax分别为15.65、10.06 mg.L-1,AUC0-t分别为45.36、25.91 mg.h.L-1,AUC0∞-分别为46.76、26.23 mg.h.L-1;试验组、对照组在血浆药代动力学参数:AUC0-t分别为512.63、532.71 mg.h.L-1,AUC0∞-分别为515.35、533.90 mg.h.L-1。脑脊液中,试验组甲氨蝶呤的Cm ax和AUC0-t、AUC0-∞均明显高于对照组(P<0.05);血浆药代动力学参数与对照组比较无显著性差异;血脑屏障透过率由4.86%提高到8.85%。结论冰片可促进甲氨蝶呤透过血脑屏障,增加其在脑脊液中的药物浓度;而不改变其血药浓度。

Objective To study the effect of borneol on the penetration of methotrexate across blood brain barrier in rabbits. Methods Twelve Japanese white rabbits were divided into 2 groups randomly, after intragastric administration of borneol 0. 7 g ·kg^-1 to the test group and 75% alcohol to the control group, 100 mg· kg^-1 of methotrexate were given to both group by intravenous injection. The concentrations of methotrexate in plasma and cerebrospinal fluid were determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated by 3P97 software. Results Pharmacokinetic parameters of test and control group were as follows： in cerebrospinal fluid, AUC0-t were 45. 36 and 25.91 mg· h · L^-1 , AUC0-∞ were 46.76 and 26.23 mg· h· L^-1 ,Cmax were 15.65 and 10. 06 mg ·L^-1 ; in plasma, AUC0-t were 512.63 and 532.71 mg ·h · L^-1,AUC0-∞ were 515.35 and 533.90 mg· h· L^-1. Pharmacokinetic parameters AUC0-t ,AUC0-∞ and C of test group in cerebrospinal fluid increased significantly compared with those of the control group （ P 〈 0. 05 ） , while not much difference of pharmacokinetic parameters in plasma between these two groups. The permeability of blood brain barrier was increased obviously from 4. 86% to 8.85%. Conclusion Borneol can enhance the penetration of methotrexate through the blood brain barrier, resulting in the rising level of methotrexate into cerebrospinal fluid, without any effect to the pharmacokinetics in plasma.