氯沙坦及其代谢物在汉族健康人体内药动学研究

 目的 研究氯沙坦及其代谢产物2-丁基-4-氯-1-2’-(1H-四唑-5-基）1，1‘-联苯基]-4-基]甲基]-lH一咪唑-5-羧酸（E-3174）在中国汉族健康受试者体内的药动学。方法 10名健康受试者，男女各半，口服氯沙坦钾片50 mg，定时采血，用HPLC荧光法测定氯沙坦及其代谢物E-3174血药浓度，DAS2.0软件程序进行数据处理并采用SPSS13.0软件进行统计学分析。结果 氯沙坦和E-3174的主要药动学参数如下：ρ_max分别为( 351±167)，( 241±60) μg·L^-1; t_max分别为(1.35±1.06)，(3.60±1.68) h；t1/2分别为(0.82±0.40)，(4.66±1.10) h；AUC_0-24分别为(498±172)，(1 853±194) μg ·h·L^-1；AUC_0-∞分别为(523±184)，(1 960±182) μg ·h·L^-1。结论 氯沙坦及其代谢物E-3174的药动学特征和参数在个体间存在较大差异，临床治疗中应实行个体化给药方案。

Pharmacokinetics of Losartan and Its Metabolite in Han Healthy Volunteers

OBJECTIVE To investigate the pharmacokinetics of losartan and its major metabolite， E-3174， in Chinese Han healthy volunteers. METHODS Ten healthy volunteers (5 male and 5 female) were given 50 mg losartan potassium tablets. Blood samples were taken at predetermined time. The concentrations of losartan and E-3174 in plasma were determined by HPLC-fluorescence(FLU) method. The pharmacokinetic parameters were calculated by DAS2.0 software and compared by SPSS13.0 software. RESULTS The pharmacokinetic parameters of losartan and E-3174 were as follows: ρ_max ( 351±167) and ( 241±60) μg·L^-1, tmax (1.35±1.06) and （3.60±1.68）h, t 1/2 (0.82±0.40) and (4.66±1.10) h, AUC_0-24 （498±172） and （1 853±194）μg ·h·L^-1, AUC_0-∞ (523±184) and (1 960±182) μg ·h·L^-1. CONCLUSION The pharmacokinetic characteristics and parameters of losartan and E-3174 had significant inter-individual variability. Individual dose regimens should be used in the clinical treatment.