【作者】 赵静；

【导师】 张沂；

【作者基本信息】 大连医科大学 ， 药理学， 2013， 硕士

【摘要】 目的：在前期研究的基础上，建立亚低温动物模型，研究并比较正常体温与低体温下尼莫地平在兔体内的药动学和药效学，为低体温治疗下安全合理使用尼莫地平建立科学论据。方法：5只健康同龄成年新西兰白兔，体重（2.0±0.5）kg，雄性。先测定常温下尼莫地平的药动学和药效学实验，经过2周的洗脱期后再进行亚低温下的药动学和药效学实验。常温条件实验组为A组，低体温实验组为B组。亚低体温动物模型建立采用冰块全身降温方法，将动物体温降至31±1℃，连续监测动物直肠温度，在肛温稳定20min后给药组开始给药，尼莫地平给药剂量为0.5mg/kg，在耳缘静脉缓慢注入，注射时间为1min，在给药前和给药后0.16h,0.33h,0.5h,1h,2h,4h,6h时间点于给药对侧耳缘静脉采血1.5ml，置于肝素抗凝管中。采用LC-MS/MS测定血浆药物浓度。3P97药代动力学软件处理数据，药效学测定应用彩色颅多普勒超声脑血流参数和心率。SPSS16.0软件统计学分析。结果：（1）药动学研究：A组与B组间比较，血药浓度、药时曲线下面积（areaunder curve，AUC）、分布容积（distrabution volume，Vc）、半衰期（eliminationhalf life,t1/2β)、清除率（clearance，Cl）、MRT和VRT有显著性差异。（2）药效学研究：A组与B组间比较，两种条件下平均脑血流速度均比给药前增加，低温下持续时间较长，但无统计学意义，心率无显著变化。结论：与常温比较亚低体温条件下，尼莫地平在兔体内的代谢受到影响，清除减慢，半衰期延长，血药浓度增加，AUC增大，MRT和VRT增加；药物改善脑血流作用持续时间延长，对心率无影响。更多还原

【Abstract】 Objective: On the basis of previous research, we established mild and moderatehypothermia models of animal to research and compare the pharmacokinetics andpharmacodynamics of nimodipine in rabbits under normal temperature and hypothermia.This research provided a scientific basis for safe and reasonable use of nimodipine inclinical applications with therapeutic hypothermia.Methods:5healthy male rabbits weighing2.2～2.7kg were used in the study.First,we researched the pharmacokinetics and pharmacodynamics of nimodipine innormal temperature. After two weeks of washout period,we researched thepharmacokinetics and pharmacodynamics of nimodipine in hypothermia. Normaltemperature was marked group A and hypothermia was marked group B.Group B was used ice to cool the whole body until the body temperature down to31±1℃. The animals are monitored anal temperature continuously. After the analtemperature was stable about20minutes, each group began to inject nimodipine slowlyform ear marginal vein at0.5mg/kg dose.It took1minute.1.5ml blood samples weretaken from another ear vein at0.16h,0.33h,0.5h,1h,2h,4h,6h after injection and put inheparin anticoagulant tubes.The plasma concentration of nimodipine was detected byHPLC/MS/MS. The datas were calculated by3p97pharmacokinetics software. CBFandHR were detected by transcranial doppler. SPSS16.0software was used for statisticalanalysisResults:（1）Pharmacokinetic study：Compared between A and B，the plasmadrug concentration， AUC(area under curve)，Vc（distrabution volume），t1/2β（elimination half life,)，C（lclearance），MRT and VRT were significant difference.（2）Pharmacodynamic study：Compared betweenAand B，mean cerebral blood flow was both increased in A and B.The effective time was longer in B. But there was nostatistical significance.There was no influence in HR.Conclusion: Compared with normal temperature,hypothermia had an impact onmetabolism of nimodipine in rabbits. The clearance was slower and half-life was longer.Plasma drug concentration, AUC,MRT and VRT were increased.; Nimodipine canimprove brain blood flow and the effective time was longer.There was no influence inHR.更多还原