在CYP1A1和CYP3A5基因多态性的可变性导致Granisetron间隙和接触孕妇的恶心和呕吐。

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布斯托斯毫升,赵Y,陈H, Caritis SN, Venkataramanan R

在CYP1A1和CYP3A5基因多态性的可变性导致Granisetron间隙和接触孕妇的恶心和呕吐。

药物治疗。2016年12月,36 (12):1238 - 1244。doi: 10.1002 / phar.1860。Epub 2016 12月5。

PubMed ID

27809336 (在PubMed

]

文摘

背景:恶心和呕吐影响多达90%的孕妇。Granisetron是强有力的和高度选择性5 -羟色胺受体拮抗剂,是一种有效的止吐剂。从之前的一项研究发现孕妇演示了一个大型个人间变异性granisetron曝光。Granisetron主要是代谢的细胞色素P450 (CYP) CYP1A1和CYP3A酶可能是一种代号为ABCB1的衬底的运输车。单核苷酸多态性(snp)在CYP3A种代号为ABCB1的CYP1A1,可以改变药物的代谢。摘要目的:本研究评估CYP3A4多态性的影响,CYP3A5,种代号为ABCB1的CYP1A1和在孕妇granisetron的药代动力学性质。方法:研究了16个孕妇(妊娠12周内)的时代。所有的病人有恶心和呕吐,服用granisetron 1毫克。Granisetron血浆浓度测定使用液相色谱串联质谱分析。病人的基因型决定使用TaqMan SNP基因分型检测。 The Hardy-Weinberg equilibrium was assessed by comparing observed and expected genotype frequencies, using the exact test. Intravenous granisetron clearance was used as the dependent variable for analysis of associations. RESULTS: Of 16 patients, 25% were homozygous for the allele variant CYP3A5*3 and had a significantly lower granisetron clearance and increased area under the plasma concentration-versus-time curve (AUC) compared with nonhomozygous patients. Approximately one-third of patients (n=5) were carriers for the allele variant CYP1A1*2A and had a significantly higher granisetron clearance and decreased AUC. We did not find significant differences in the AUC or clearance for any SNPs in CYP3A4 and ABCB1 genes. CONCLUSIONS: Polymorphisms in CYP3A5 and CYP1A1 account for some of the variability in systemic clearance and exposure of granisetron in pregnant women.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Granisetron	细胞色素P450 1 a1	蛋白质	人类	未知的	底物	细节