天然冰片对顺铂在C6脑胶质瘤模型大鼠体内的药动学及脑组织分布的影响

Effects of borneol on the pharmacokinetics and brain tissue distribution of cisplatin on C6 tumor bearing rat

目的:考察天然冰片对顺铂在C6脑胶质瘤模型大鼠体内药动学及脑组织分布的影响。方法:建立大鼠C6脑胶质瘤动物模型;模型大鼠随机分为3组,分别给予溶媒、冰片低剂量(35mg/ml)、冰片高剂量(140mg/ml)灌胃,灌胃后1h,尾静脉注射顺铂(10mg/kg),于注射后系列时间点(2min,5min,10min,30min,45min,1 h,2h,4h,8h)采集制备血浆及脑组织样品,测定血浆与脑组织中顺铂的浓度,计算其药动学参数。结果:血浆中,冰片高剂量与溶媒对照组比较t1/2β、Cmax显著增大(P<0.05),AUC(0-t)显著减小(P<0.05),而低剂量组与溶媒对照组比较无显著性差异;脑组织中,冰片高、低剂量组与溶媒对照组比较,AUC(0-∞)均显著性升高(P<0.05),其排列顺序为:AUC(0-∞)高>AUC(0-∞)低>AUC(0-∞)溶媒对照。结论:天然冰片可增加顺铂在C6脑胶质瘤模型大鼠脑组织的分布,提高顺铂对于脑部肿瘤的生物利用度。

The main purpose of this study was to describe the effects of bemeol on the pharmacokineties and brain tissue distribution of Cisplatin. Methods： The rats were given ig with solvent, berneol low-dose group （35 mg/ml）, borneol high-dose group （140mg/ml））, and in travenous injection Cisplatin（DDP） （10mg/kg,iv） lh after oral administrate inducer. Plasma and brain tissue samples were collected at corresponding time（0,2rain ,Smin, 10min,30min ,45rain, 1 h ,2h,4h,8h ） after intravenous injection. The concentrations of DDP on the plas ma and brain tissue in rats were determined by HPLC. Calculate the pharmaeokinetie parameters. Results： In plasma , there was obvious difference between the pharmacokinetic parameters of the Borneol high-dose group vs control group, t1/2β ,Cmax were remarkable higher （ P 〈 0.05） ,while AUC（o-1） was significant lower（ P 〈 0.05 ） ; there was no obvious difference between the pharmacokinetic parameters of the Borneol low-dose group vs control group. In brain tissue, there was also obvious difference between the pharmacokinetic parameters of the Bor ned high-dose group and Bomeol low-dose group vs control group, AUC （0-00）hish-doge, AUC（0-00）low-does were significantly larger than AUC（o-00）control（P 〈 0.05 ） and their size order was AUC（0-00）high-doge 〉 AUC〈0-00）low-doge 〉 AUC（0-00 ）control. Conclusion： The bomeol has the enhancing effect on absorption and brain tissue distribution, and improving effect on bioavailability of DDP on C6 tumor bearing rat.