兰索拉唑在正常及溃疡模型家兔体内药代动力学研究  

Pharmacokinetics Study of Lansoprazole between Gastric Ulcer and Normal Rabbits

作　　者：韩强[1] 潘桂玲[1] 张永文[1] 

机构地区：[1]徐州医学院附属医院药剂科,江苏徐州221002

出　　处：《药学与临床研究》2011年第1期22-25,共4页Pharmaceutical and Clinical Research

基　　金：江苏省临床药学研究奥赛康基金(P200806)

摘　　要：目的：建立高效液相色谱法分析兔血浆中兰索拉唑的含量,并比较兰索拉唑在正常及溃疡模型家兔体内药代动力学行为的差异。方法：家兔于20℃水中浸泡8小时建立胃溃疡模型,耳缘静脉给予兰索拉唑注射剂后,分别在不同时间点收集血样,HPLC法测定,采用DASS2.0软件计算给药后的药物动力学参数。结果：兰索拉唑浓度在20~2000 ng.mL-1范围内线性关系良好,最低检测浓度为20 ng.mL-1。低、中、高3个浓度的提取回收率均大于85%,批内、批间相对标准差低于10%。与正常兔比较,溃疡模型家兔给予兰索拉唑药物后体内AUC（0-6.5）明显增加[（916.84±338.61）vs（522.72±172.16）μg.h.L-1,P〈0.05]、体内平均滞留时间延长MRT（0-6.5）[（0.824±0.203）vs（0.69±0.13）h,P〈0.05]、血浆消除半衰期增大[（0.88±0.44）vs（0.53±0.28）h,P〈0.05]、血浆清除率显著减小[（2.74±1.70）vs（6.23±2.21）L.h-1,P〈0.05]、最大血药浓度增大[（1091.31±348.94）vs（682.20±234.56）μg.L-1,P〈0.05]。结论：兰索拉唑在溃疡模型家兔与正常兔之间存在明显的药动学差异。Objective： To establish an HPLC method for the determination of lansoprazole in rabbits and investigate the pharmacokinetic differences of lansoprazole between gastric ulcer and normal rabbits in vivo.Methods： Rabbits were soaked in the water at 20 ℃ for 8 hours to cause gastric ulcer.Lansoprazole injection was given through an auricular vein.Blood samples were collected at the given time points.Contents of lansoprazole in gastric ulcer and normal rabbits were assayed by HPLC-DAD method.The pharmacokinetic parameters were analyzed by double-compartmental method（DAS2.0）.Results： The resulted data of normal and gastric ulcer rabbits after lansoprazole were（522.72±172.16） μg·h·L-1 and（916.84±338.61） μg·h·L-1 for AUC（0-6.5）;（0.69±0.13） h and（0.824±0.203） h for MRT（0-6.5）,（0.53±0.28） h and（0.88±0.44） h for t1/2;（0.34±0.08） h and（0.443±0.08） h for tmax;（6.23±2.21） h·L-1 and（2.74±1.70） h·L-1 for CL;（682.20±234.56） μg·L-1 and（1091.31±348.94） μg·L-1 for Cmax,respectively.The results indicated that t1/2,MRT（0-6.5）,Cmax and AUC（0-6.5） of Lansoprazole were significantly enhanced when compared with the normal rabbits.Conclusion： The results indicate that the pharmacokinetic profiles of Lansoprazole were different between gastric ulcer and normal rabbits.

关 键 词：兰索拉唑 胃溃疡 药代动力学 家兔 

分 类 号：R965[医药卫生—药理学]