间隔改变高职院校学前教育专业醋酸氟卡尼管理后,有和没有coadministered帕罗西汀,与细胞色素P450 2 d6基因型:数据从一个非盲、两年期,单序列交叉研究在健康韩国男性受试者。

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Lim KS,张成泽IJ,金正日BH,金正日J,全司法院,Tae YM,彝族,设计年代,曹司法院,胫骨SG, KS

其他。2010年4月,32 (4):659 - 66。doi: 10.1016 / j.clinthera.2010.04.002。

PubMed ID

20435235 (在PubMed

]

文摘

背景:醋酸氟卡尼是一个类Ic antiarrythmic剂代谢的细胞色素P450 (CYP) 2 d6同工酶。先前的非盲、-周期,单序列交叉研究在健康韩国男性志愿者发现氟卡尼的药物代谢动力学情况差异与CYP2D6野生型等位基因和CYP2D6 * 10个等位基因,以及不同的药代动力学相互作用氟卡尼和基因型之间的CYP2D6抑制剂帕罗西汀组。目的:本研究评估QTc-interval改变单一口服剂量的氟卡尼管理后,没有帕罗西汀,在与CYP2D6基因多态性的关系。方法:这是一个后续的药代动力学研究和使用的数据来自同一组健康的韩国男性志愿者。受试者按CYP2D6基因型分组如下:CYP2D6 * 1 / * 1或CYP2D6 * 1 / * 2(组1、广泛的代谢);CYP2D6 * 1 / * 10(组2,中间代谢);和CYP2D6 * 10 / CYP2D6 * 010或* / * 36(组3,代谢不佳)。200毫克氟卡尼是在天1(第1期);后7天,洗脱期,主题收到帕罗西汀20毫克每天从8到14天,一旦和氟卡尼在15天200毫克(阶段2)。在第1和15天,连续12导ecg之前得到氟卡尼剂量1,1.5、2、2.5、3、4、6、8、12,给药后24小时。基线ecg得到在同一时间点天1和14。 Machine-read changes in the QT interval corrected using the Fridericia formula (QTcF) and manually read changes in the QT interval individually corrected using mixed-effects modeling (QTcI) from time-matched baseline were analyzed by genotype and by period (baseline and paroxetine-inhibited state). The QRS duration and JTc interval (QTcF - QRS) were also determined. RESULTS: Twenty-one healthy volunteers (mean [SD] age, 24.5 [3.0] years; mean height, 173.5 [4.6] cm; mean weight, 69.1 [4.5] kg), 7 in each group, were enrolled in and completed the study. In period 1, all genotype groups had significant increases from time-matched baseline in both the QTcF interval (group 1:17.4 milliseconds [90% CI, 9.9-24.9], P < 0.001; group 2: 11.1 milliseconds [90% CI, 7.9-14.3], P = 0.013; and group 3: 20.5 milliseconds [90% CI, 12.8-28.2], P < 0.001) and the QTcI interval (group 1:15.4 milliseconds [90 % CI, 8.0-22.9], P = 0.001; group 2: 9.1 milliseconds [90% CI, 6.5-11.8], P = 0.030; and group 3:16.4 milliseconds [90% CI, 9.3-23.5], P = 0.001); the extent of increase did not differ significantly between groups. In groups 1 and 2, the least squares mean difference between period 1 and period 2 was statistically significant for the change in QTcF interval (6.5 milliseconds [90 CI, 3.2-9.8], P = 0.002; and 6.7 milliseconds [90% CI, 3.6-9.7], P = 0.001, respectively) and QTcI interval (6.9 milliseconds [90% CI, 4.1-9.8], P < 0.001; and 5.8 milliseconds [90% CI, 3.4-8.3], P < 0.001). In group 3, the least squares mean difference between period 1 and period 2 was statistically significant for the change in QTcI interval (3.9 milliseconds [90% CI, 1.3-6.5], P = 0.015) but not for the change in QT cF interval. The changes in QRS duration did not differ significantly by genotype or period. Consistent with the findings for the QTc interval, the least squares mean difference between period 1 and period 2 was statistically significant for the change in JTc interval in groups 1 and 2 (6.9 milliseconds [90% CI, 3.7-10.2], P = 0.001; and 5.4 milliseconds [90% CI, 2.7-8.2], P = 0.001, respectively) but not in group 3. CONCLUSION: The extent of drug interaction between flecainide and paroxetine, as reflected in the change in QTc interval (used as a pharmacodynamic biomarker), was influenced by the CYP2D6*10 allele in these healthy Korean male volunteers.

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
氟卡尼	细胞色素P450 2 d6	蛋白质	人类	未知的	底物抑制剂	细节