黄豆苷元对不同基因型健康受试者氯沙坦药代动力学的影响  

Effect of Daidzein on Pharmacokinetics of Losartan in Healthy Volunteers with Different Genotypes

作　　者：肖昌琼[1] 陈锐[1] XIAO Changqiong;CHEN Rui(The First People′s Hospital of Chenzhou City,Chenzhou,Hunan 423000,P.R.China)

机构地区：[1]湖南省郴州市第一人民医院中心医院药学部临床药学科,湖南彬州423000

出　　处：《中国药业》2021年第4期30-34,共5页China Pharmaceuticals

基　　金：湖南省中医药科研计划项目[2021139];湖南省郴州市级重点研发及技术创新引导专项[ZDYF2020091];湖南省郴州市第一人民医院教学改革课题[CJG2020-8]。

摘　　要：目的探讨黄豆苷元对不同基因型健康受试者氯沙坦药代动力学的影响。方法筛选中国男性健康受试者18名(CYP2C9*1/*1、CYP2C9*1/*3、CYP2C9*1/*13基因型各6名)。执行双周期、自身前后对照方案,第一阶段随机分为对照组和试验组,受试者分别口服黄豆苷元片或安慰剂15 d,第15天两组受试者均口服氯沙坦50 mg;经过14 d洗脱期后交叉重复试验。均分别于口服氯沙坦后0,0.25,0.5,0.75,1,1.5,2,2.5,3,4,6,8,12 h时采集静脉血,并采用高效液相色谱串联质谱法测定血浆样品中氯沙坦及其代谢产物E-3174的药代动力学参数。结果两组受试者均完成试验,无药品不良反应/事件发生。试验组中,与CYP2C9*1/*1亚组比较,CYP2C9*1/*3亚组和CYP2C9*1/*13亚组受试者血浆E-3174峰浓度(C_(max))显著降低(P<0.05);对照组3个亚组受试者血浆E-3174的C_(max)无显著差异(P>0.05);试验组和对照组3个亚组受试者血浆氯沙坦的C_(max)无显著差异(P>0.05);与对照组比较,试验组CYP2C9*1/*1基因型受试者血浆E-3174的C_(max)显著降低(P<0.05)。结论黄豆苷元对CYP2C9*1/*1正常基因型健康受试者氯沙坦的代谢无显著影响;对于CYP2C9*1/*3及*13突变等位基因型健康受试者,可影响氯沙坦代谢生成E-3174而降低后者的血药浓度,其临床意义有待进一步证实。Objective To investigate effect of daidzein on the pharmacokinetics of losartan in healthy volunteers with different genotypes.Methods Totally 18 Chinese healthy male volunteers with the genotypes of CYP2 C9*1/*1,CYP2 C9*1/*3,CYP2 C9*1/*13 were enrolled in this study with six volunteers each.The experiment was conducted in a 2-period crossover study and self-control study.In the first stage,the volunteers were randomly divided into the control group and the experimental group,the volunteers in the experimental group took Daidzein Tablets for 15 d,and the volunteers in the control group took placebo for 15 d,and the volunteers in both groups took 50 mg of losartan orally on the 15 th day,the cross and repeated tests were carried out after 14 d washing out period.Venous blood samples were collected at 0,0.25,0.5,0.75,1,1.5,2,2.5,3,4,6,8 and 12 h after oral administration of losartan.The pharmacokinetic parameters of losartan and its metabolite E-3174 in plasma samples were determined by high-performance liquid chromatography-mass spectrometry(HPLC-MS).Results The volunteers in the two groups completed the trial,no adverse drug reactions/events occurred.In the experimental groups,the C_(max)of plasma E-3174 in CYP2 C9*1/*3 subgroup and CYP2 C9*1/*13 subgroup was significantly lower than that in CYP2 C9*1/*1 subgroup(P<0.05).There was no significant difference in C_(max) of plasma E-3174 among the three subgroups(P>0.05).In the experimental groups,there was no significant difference in C_(max) of plasma E-3174 among the three subgroups(P>0.05).There was no significant difference in C_(max)of losartan between the three subgroups of the experimental groups and the three subgroups of the control groups(P>0.05).Compared with that in the control group,the C_(max)of plasma E-3174 in volunteers with CYP2 C9*1/*1 genotype in the experimental group was significantly lower(P<0.05).Conclusion Daidzein has no significant effect on the metabolism of losartan in healthy volunteers with CYP2 C9*1/*1 genotype,but it can affect the m

关 键 词：黄豆苷元 基因多态性 药代动力学 氯沙坦 E-3174 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]