种代号为ABCB1的影响和CYP3A5基因多态性在健康志愿者喹硫平的药物代谢动力学情况。
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Kim KA - Joo黄建忠,李嗯,公园司法院
种代号为ABCB1的影响和CYP3A5基因多态性在健康志愿者喹硫平的药物代谢动力学情况。
Pharmacogenet基因组学。2014年1月,24 (1):35-42。doi: 10.1097 / FPC.0000000000000020。
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24240480 (在PubMed]
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背景和目的:喹硫平是一种非典型抗精神病药物用于治疗精神分裂症和急性躁狂发作。喹硫平是由CYP3A酶代谢包括CYP3A5和衬底的22,一种代号为ABCB1的射流的药物转运蛋白编码基因。我们种代号为ABCB1的评估的影响(c。1236 c > T (rs1128503), c。2677 g > T / A (rs2032582), c。3435 c > T (rs1045642)]和CYP3A5 * 3 (> 6986 G)多态性(rs776746)喹硫平在人体内的药物动力学。材料与方法:四十岁健康男性个人注册,和种代号为ABCB1的他们和CYP3A5多态性进行了评估。单剂量100毫克喹硫平后,喹硫平的血浆浓度测定24 h和药代动力学进行了分析。种代号为ABCB1的结果:包括c多态性。1236 c > T, c。2677 g > T / A, c。3435 c > > T并不影响等离子体水平的喹硫平,没有种代号为ABCB1的之间的基因型差异及其药代动力学参数组。 However, the CYP3A5*3 polymorphism significantly affected the plasma level of quetiapine and its pharmacokinetics. The peak plasma concentration of quetiapine was 208.39 ng/ml for CYP3A5*1/*1, 243.46 ng/ml for CYP3A5*1/*3, and 332.94 ng/ml for CYP3A5*3/*3 (P=0.0118). The mean AUC(inf) (area under the time vs. concentration curve from 0 to infinity) value was 627.3, 712.77, and 1045.29 ng h/ml, respectively (P=0.0017). CONCLUSION: The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics. These findings suggest that the CYP3A5 genetic polymorphism affects the disposition of quetiapine and provide a plausible explanation for interindividual variation in the disposition of this drug.