Losartan 在健康人体中药效学和药代学的研究

目的：探讨Losartan在体内对肾素-血管紧张素系统的影响以及国人体内losartan代谢过程，为解释其降压机理及临床合理用药提供参考；方法：以健康受试者为研究对象，采用随机、双盲给予药物和安慰剂，观察受试者血压和体内肾素的变化，以及losartan及其代谢产物在体内代谢过程。结果：血压在用药后6h内下降幅度较大，而肾素活性在8h左右升高幅度最大。以及losartan在服药后3h，药物浓度达到高峰，而其代谢产物EXP3174在服药后8h血药浓度达高峰。血浆肾素活性和EXP3174的AUC0-24成正相关。结论：losartan的降低血压与其代谢产物EXP3174作用直接相关，在降压幅度最大时，肾素的活性也达到最高点。这可能与血管紧张素系统的自身调节有关。

The Investigation of Pharmacodynamics and Pharmacokinetics of Losartan in Chinese Subjects

To explore the effect of losartan on the rennin-agiotensin system and its metabolism in Chinese subjects,and to further explain its mechanism of hypotension,the Chinese subjcts were registered,and randomly ,double blindly given with losartan and placebo.Changes of blood pressure and rennin activity ,and process of metabolism of losartan and its metablite EXP3174 were observed.Results shown that blood pressure were deeply decreased in 6h after administration ,while the renin activity was higher in 8h.The time of Cmax of losartan was 3h,and EXP3174 was 8h.There are consistent with renin activity and EXP3174 AUC 0-24 .In conclusion,The hypotension of losartan was mainly realted to EXP3174,the highest of the hypotension was consisted with the plasma renin activity,which may have something to do with the feedback of RAS