阿利沙坦酯与氯沙坦钾在健康受试者的药代动力学研究  

Pharmacokinetics and safety of allisartan and losartan potassium in healthy volunteers

作　　者：邓超 阳国平[2] 冯泽英 崔畅 杨双[2] 王正梅 杨晓燕 黄洁[2] DENG Chao;YANG Guo-ping;FENG Ze-ying;CUI Chang;YANG Shuang;WANG Zheng-mei;YANG Xiao-yang;HUANG Jie(Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,Hunan Province,China;Center of Clinical Pharmacology,the Third Xiangya Hospital,Central South University,Changsha 410013,Hunan Province,China)

机构地区：[1]中南大学湘雅药学院,湖南长沙410013 [2]中南大学湘雅三医院临床药理中心,湖南长沙410013

出　　处：《中国临床药理学杂志》2021年第24期3358-3362,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究阿利沙坦酯和氯沙坦钾在中国健康受试者的药代动力学。方法按单中心、单剂量、随机、开放、两周期交叉的试验方案,入选16例健康受试者,随机交叉分别单次口服阿利沙坦酯240 mg或氯沙坦钾100 mg,用高效液相色谱-液相质谱联用(HPLC-MS/MS)法测定血浆中EXP3174的浓度,SAS 9.4软件计算药代动力学参数。结果阿利沙坦酯代谢产物EXP3174的药代动力学参数如下:C_(max)为(1168.40±573.40)μg·L^(-1);AUC_(0-48 h)为(8702.46±3213.45)h·μg·L^(-1);AUC_(0-∞)为(8977.43±3202.81)h·μg·L^(-1);氯沙坦代谢产物EXP3174的主要药代动力学参数如下:C_(max)为(1186.40±418.07)μg·L^(-1);AUC_(0-48 h)为(6143.33±1420.42)h·μg·L^(-1);AUC_(0-∞)为(6319.21±1456.05)h·μg·L^(-1),两种药物活性代谢物EXP3174的C_(max)、AUC_(0-48 h)和AUC_(0-∞)参数的几何均值比值(阿利沙坦酯/氯沙坦)分别为77.76%~102.42%,120.26%~143.80%和121.49%~144.21%。结论阿利沙坦酯240 mg与氯沙坦钾100 mg相比,其人体内活性代谢产物EXP3174的AUC_(0-48 h)和AUC_(0-∞)明显高于后者,且半衰期更长,提示其降血压作用可能更为持久。Objective To compare the pharmacokinetics of allisartan and losartan potassium in Chinese healthy volunteers,so as to provide information for the rational use of allisartanaxetil in clinic.Methods According to the single-center,single-dose,randomized,openlabel,crossover-design trial,16 healthy volunteers were randomly divided into two groups.The concentration of EXP3174 in plasma was determined by high performance liquid chromatography-liquid chromatography-mass spectrometry(HPLC-MS/MS),and the pharmacokinetic parameters were calculated by SAS9.4 software.ResultsThe pharmacokinetic parameters of EXP3174 after administration of allisartan were as follows:C_(max)(1168.40±573.40)μg·L^(-1),AUC_(0-48h)(8702.46±3213.45)h·μg·L^(-1),AUC_(0-∞)(8977.43±3202.81)h·μg·L^(-1);and the main pharmacokinetic parameters of losartan metabolite EXP3174 were as follows:C_(max)(1186.40±418.07)μg·L^(-1);AUC_(0-48h)(6143.33±1420.42)h·μg·L^(-1);AUC_(0-∞)was(6319.21±1456.05)h·μg·L^(-1).The geometric mean ratios of C_(max),AUC_(0-48 h)and AUC_(0-∞)parameters of EXP3174(allisartan/losartan)were 77.76%-102.42%,120.26%-143.80%and 121.49%-144.21%.Conclusion Compared with losartan potassium of 100 mg,the AUC_(0-48 h)and AUC_(0-∞)of EXP3174,the active metabolite of allisartan 240 mg are significantly higher and the half-time is longer,suggesting that the effect of allisartan on blood pressure may be more lasting.

关 键 词：阿利沙坦酯 氯沙坦钾 药代动力学 

分 类 号：R97[医药卫生—药品]