阿托伐他汀对氯沙坦及其代谢物EXP 3174在大鼠体内药物代谢动力学的影响  

Influence of atorvastatin on the pharmacokinetics of losartan and EXP 3174 in rats

作　　者：解朝永[1] 解雷[2,3] 车媛媛[1] 彭庆奎[1] 包金丽[1] 

机构地区：[1]枣庄市立医院心内一科,山东枣庄277100 [2]第二军医大学,上海200430 [3]上海吴孟超肿瘤医学中心宁波肿瘤医院,浙江宁波315201

出　　处：《中南药学》2016年第5期484-488,共5页Central South Pharmacy

摘　　要：目的研究联用氯沙坦和阿托伐他汀之后,阿托伐他汀对氯沙坦及其代谢物EXP 3174在大鼠体内药物代谢动力学的影响。方法 24只雄性SD大鼠,随机分为2组,其中A组灌胃给药氯沙坦9 mg·kg-1,B组灌胃给予阿托伐他汀和氯沙坦,给药剂量分别为1 mg·kg-1和9 mg·kg-1。在不同时间点取血,采用LC-MS测定氯沙坦及其代谢物EXP 3174的血药浓度,计算并比较氯沙坦及其代谢物EXP 3174的药物代谢动力学参数。结果与单独给药组相比,药物联用组氯沙坦及其代谢物EXP 3174的药物代谢动力学参数发生了明显的变化,其中氯沙坦的最大血药浓度和血浆曲线下面积分别增加了55.5%和53.9%(P<0.05)。而代谢物的最大血药浓度明显下降(P<0.05),说明氯沙坦的代谢受到了明显的抑制。结论阿托伐他汀与氯沙坦联用之后,会对氯沙坦和代谢物EXP 3174的药物代谢动力学产生明显的影响,本研究对氯沙坦和阿托伐他汀联合用药具有一定的指导作用,可以避免临床药物不良相互作用的发生。Objective To investigate the influence of atorvastatin on the pharmacokinetics of losartan and its metabolite EXP 3174 in rats. Methods Totally 24 male rats were equally randomized to 2 groups, including the losartan-only group （A） and the losartan and atorvastatin group （B）. Group A were administered an oral dose of 9 mg · kg -1, and group B were administered an oral dose of atorvastatin （1 mg · kg -1）, and losartan （9 mg · kg -1）. Blood samples were collected into a beparinized tube via the oculi chorioideae vein at different time points after the drug administration. The plasma concentration of losartan and EXP 3174 were determined by LC-MS. Finally the pharmacokinetic profiles of losartan and EXP 3174 were compared. Results The peak plasma concentration and the area under the plasma concentration-time curve of losartan were significantly （P 〈 0.05） increased by 55.5% and 53.9%, respectively, by atorvastatin compared with those in the control group. While the peak plasma concentration of EXP 3174 decreased significantly compared with that of the control group （P 〈 0.05）, indicating that the metabolism of losartan was significantly inhibited. Conclusion Atorvas- tatin can influence the pharmacokinetics of losartan and EXP 3174 when atorvastatin and losartan are used con- comitantly. This study can be used for clinical medication guidance of losartan and atorvastatin to avoid adverse reactions.

关 键 词：氯沙坦 阿托伐他汀 药物代谢动力学 药物相互作用 

分 类 号：R96[医药卫生—药理学]