| 张培哲,曹邦明,李佳俊,等.达比加群在家兔中的药代动力学及其对实验室检查的影响[J].安徽医药,2019,23(3):449-453. |
| 达比加群在家兔中的药代动力学及其对实验室检查的影响 |
| Pharmacokinetics of Dabigatran in rabbits and its effect on laboratory assessment |
| 投稿时间：2017-02-20 |
| DOI： |
| 中文关键词: 达比加群的药代动力学是可预测的且在体内抗凝效果无时间延迟 APTT不适合作为定量检测达比加群的指标,但其值显著升高提示高浓度的达比加群 TT可作为达比加群的定性指标 ECA可在一定程度上作为达比加群定量的指标,但需进一步的研究。 关键词:达比加群 药代动力学 蛇静脉酶发色底物法测定 部分凝血酶原时间 凝血酶时间 |
| 英文关键词: Dabigatran Pharmacokinetics ECA APTT TT |
| 基金项目: |
|
| 摘要点击次数: 2263 |
| 全文下载次数: 492 |
| 中文摘要: |
| 目的 通过在新西兰大白兔中单剂量服用达比加群酯,对比不同时间点的达比加群血药浓度变化、不同血药浓度时的实验室检查结果,探讨达比加群的药代动力学特征及其对实验室检查结果的影响。 方法 18只新西兰大白兔采用随机数字表法分为5 mg/kg组、10 mg/kg组和对照组三组,每组6只,分别灌胃5 mg/kg、10 mg/kg达比加群酯溶液和等体积的溶剂,于给药前,给药后0.5、1、1.5、2、3、4、6、8、12、24 h取血,通过液相色谱-串联质谱法(LC-MS/MS)检测达比加群血药浓度计算药代动力学参数并分析组间差异；通过检测达比加群浓度(蛇静脉酶发色底物法测定,ECA)、部分凝血酶原时间(APTT)、凝血酶时间(TT),与LC-MS/MS结果做相关性分析,同时对ECA与LC-MS/MS进行Bland-Altman偏倚性分析。 结果 达比加群在各实验组中药代动力学参数:5 mg/kg组:tmax=(2.42±0.66)h、Cmax=(131.07±49.95)ng/mL、AUC0→t=(814.56±366.86)ng·h-1·mL-1、AUC0→∞=(902.79±426.86)ng·h-1·mL-1、MRT=(5.69±1.74)h、t1/2=(8.12±1.98)h；10 mg/kg组:tmax=(2.83±1.13)h、Cmax=(309.99±189.12)ng/mL、AUC0→t=(1 732.26±605.15)ng·h-1·mL-1、AUC0→∞=(1887.63±616.99)ng·h-1·mL-1、MRT=(5.69±1.83)h、t1/2=(8.47±2.87)h,两实验组tmax、MRT和t1/2均差异无统计学意义(P>0.05)。实验室检查结果:与对照组相比,给药后TT-时间曲线随药-时曲线有类似的变化。APTT与达比加群呈低度相关(R2=0.224)；TT与达比加群浓度呈高度相关(R2=0.780)但有过高的敏感性；ECA检测达比加群的血药浓度呈高度相关(R2=0.882),Bland-Altman偏倚性分析提示ECA低估药物浓度。 |
| 英文摘要: |
| Objective To compare the plasma concentrations of Dabigatran at different time points and the effect of laboratory assessment at different plasma concentrations after oral administration single dose of Dabigatran etexilate in the New Zealand White rabbits and investigate the pharmacokinetics profile of Dabigatran and its effect on laboratory test results. Methods 18 New Zealand White rabbits were divided randomly into three groups:5 mg/kg group,10 mg/kg group and control group.Then 5 mg/kg,10 mg/kg of dabigatran etexilate and an equal volume of solvent was administered via oral gavage,respectively.The blood samples were collected before administration and 0.5,1,1.5,2,3,4,6,8,12,4 h after dosing.The blood samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and pharmacokinetic parameters were calculated and t-test was used to analyze the differences between groups.Then the correlations between the results of laboratory tests of ECA,APTT,TT and the results of LC-MS/MS were analyzed.The Bland-Altman bias plots analysis were performed by ECA and LC-MS/MS. Results The pharmacokinetic parameters of Dabigatran in each experimental group:5 mg/kg group:tmax=(2.42±0.66) h,Cmax=(131.07±49.95)ng/mL,AUC0→t=(814.56±366.86)ng·h-1·mL-1,AUC0→∞=(902.79±426.86)ng·h-1·mL-1,MRT=(5.69±1.74)h,t1/2=(8.12±1.98)h;10 mg/kg group:tmax=(2.83±1.13)h,Cmax=(309.99±189.12)ng/mL,AUC0→t=(1 732.26±605.15)ng·h-1·mL-1,AUC0→∞=(1 887.63±616.99)ng·h-1·mL-1,MRT=(5.69±1.83)h,t1/2=(8.47±2.87)h.There was no significant difference in tmax,MRT and t1/2 between the two experimental groups (P>0.05).Laboratory assessment results:compared with the control group,the TT-time curve after administration showed a similar change with the drug-time curve.APTT and Dabigatran concentration was with weak correlation (R2=0.224).TT and dabigatran concentration was strong correlated(R2=0.780) with high sensitivity.ECA and dabigatran concentration was high correlated(R2=0.882) and the Bland-Altman bias plots analysis suggested that ECA underestimates the drug concentration. Conclusion The pharmacokinetics of dabigatran is predictable and there is no lag time between plasma concentrations and anticoagulant effect in vivo. APTT cannot be used as a quantification of Dabigatran test.However,the significant elevation suggests a high concentration of Dabigatran.TT can be used as a qualitative indicator of Dabigatran.To some extent,ECA can be used as a quantification of Dabigatran,which further study is needed. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
