CYP2D6 * 10对美西律的影响药物动力学在健康成人志愿者。

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大谷M,福田T, Naohara M, Maune H, C邮寄,山本,Azuma J

CYP2D6 * 10对美西律的影响药物动力学在健康成人志愿者。

欧元中国新药杂志。2003年9月,59 (5 - 6):395 - 9。doi: 10.1007 / s00228 - 003 - 0656 - 5。Epub 2003年8月23日。

PubMed ID

12937870 (在PubMed

]

文摘

目的:与人类肝微粒体体外研究表明,氧化转换的美西律(MX)其代谢物CYP2D6酶催化和微粒体明显受损,CYP2D6 * 10 / * 10基因型。因此,我们研究了CYP2D6 * 10等位基因的影响在日本臣民MX药物动力学。方法:研究对象与CYP2D6 * 1 / * 1(集团* 1 / * 1;n = 5), CYP2D6 * 10 / * 10(组* 10 / * 10;n = 6)和CYP2D6 * 5 / * 10(5组* / * 10;n = 4)基因型收到一个200毫克剂量的MX。血浆和尿MX及其代谢物(p-hydroxymexiletine(榜单)hydroxymethylmexiletine(嗯)和N-hydroxymexiletine (NHM))测定的高效液相色谱法。结果:平均曲线下的面积(AUC)和t(1/2)的MX显著(P < 0.05)高于CYP2D6 * 10 / * 5组(AUC 11.23 + / - -3.05微g.h /毫升;t (1/2) 15.5 + / - -3.2 h)比CYP2D6 * 1 / * 1 (AUC 5.53 + / - -1.01微g.h /毫升;t (1/2) 8.1 + / - -1.6 h)和CYP2D6 * 10 / * 10 (AUC 7.32 + / - -2.36微g.h /毫升; t(1/2) 10.8+/-2.8 h) groups, but there was no significant difference between the CYP2D6*1/*1 and CYP2D6*10/*10 groups. The maximum plasma concentration of MX was not significantly different among the three groups. The values of urinary excretion of PHM and HMM in the CYP2D6*1/*1 group were significantly ( P<0.05) higher than those in the CYP2D6*10/*10 and CYP2D6*5/*10 groups, but there was no significant difference in that of NHM among the three groups. Clearance of MX in the CYP2D6*5/*10 subjects was comparable to that in the poor metabolizers described previously. CONCLUSION: The present findings demonstrated that carriers of the CYP2D6*10 allele showed a decreased clearance of MX. Subjects with CYP2D6*5/ *10 showed significantly ( P<0.05) increased plasma levels of MX, and homozygotes for CYP2D6*10 also showed an increase, although to a lesser extent. Thus, the CYP2D6*10 allele plays an important role in MX pharmacokinetics.

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
美西律	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节