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

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...

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

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_maxof 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_maxof 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_maxof 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 metabolism of losartan to E-3174 and reduce the plasma concentration of E-3174 in healthy volunteers with CYP2 C9*1/*3 and its variant(CYP2 C9*13)genotypes.However,its clinical significance needs to be further confirmed.