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作 者:张玲非[1] 刘敏彦[2] 潘会敏[1] 师哲[1] 王鑫国[1] 牛丽颖[1]
机构地区:[1]河北医科大学中医学院河北省实验动物重点实验室,河北石家庄050091 [2]石家庄以岭药业股份有限公司,河北石家庄050035
出 处:《中国药理学通报》2011年第10期1462-1466,共5页Chinese Pharmacological Bulletin
基 金:河北省自然科学基金资助项目(NoC2010000498)
摘 要:目的比较白芍总苷(TGP)在免疫性肝损伤大鼠和正常大鼠体内药动学参数的异同,为临床制定给药方案提供参考。方法采用猪血清腹腔注射法建立大鼠免疫性肝损伤模型,以HPLC法测定模型大鼠和正常大鼠灌胃给予3个剂量白芍总苷后15、30、60、90、120、150、180、240、360、480、720min血浆中芍药苷和芍药内酯苷浓度,根据药时曲线计算药动学参数,采用SPSS 11.5软件分析各组各剂量间药动学参数异同。结果与正常组相比,模型组大鼠体内白芍总苷的Cmax、AUC0-t和AUC0-∞明显增大,Tmax明显提前,T12明显延长;各剂量间白芍总苷Tmax和T21没有差异,剂量与Cmax、AUC0-t和AUC0-∞有一定的相关性。结论肝损伤大鼠对TGP的吸收速度较正常大鼠快,吸收量较大,消除较慢,提示临床要针对不同的机体状态,设计合理安全的剂量,以免给药量过大引起蓄积和毒性反应。Aim To compare pharmacokinetics of total glucosides of paeony(TGP) in immunological liver injured rats and normal rats to provide evidence for making dosage regimen in clinic.Methods Pig serum intraperitoneal injection was used to establish immunological liver injured rats.Three dosages of TGP were orally administered to normal and model animals.With HPLC,the concentration of paeoniflorin and albiflorin in plasma was measured at times of 15,30,60,90,120,150,180,240,360,480 and 720 min after dosing was determined.According to concentration-time curve the parameters were calculated.Carry out data analysis between groups with SPSS 11.5.Results Compared with normal group,Cmax,AUC0-t and AUC0-∞ of TGP in model group significantly increased,Tmax advanced,T12 prolonged;among three dosages,Tmax and T12 hadn't difference,and dosage with Cmax,AUC0-t and AUC0-∞ had determinate correlation.Conclusions TGP in immunological liver injured rats is absorbing more rapidly than normal rats,absorbing dose is larger,and it eliminates more slowly,suggesting that the dose in clinic need to be designed reasonably and safely to avoid accumulation and toxicity caused by overdose.
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