Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias.
Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias.
复制标题
心律失常患者慢性氟卡尼和奎尼丁之间的立体选择性遗传决定相互作用。
DOI：
10.1111/j.1365-2125.1992.tb04035.x
复制
发表时间：
1992
影响因子：
3.4
通讯作者：
Roden,DM
中科院分区：
文献类型：
--
作者：
Birgersdotter,UM;Wong,W;Turgeon,J;Roden,DM
1.最近的报道表明，P450IID6基因多态性在单剂量抗心律失常氟卡胺的立体选择性处置中起作用。2.在本研究中，我们评价了在慢性氟卡胺治疗心律失常患者的基础上加用小剂量奎尼丁的效果。3.在5名广泛代谢物患者中，奎尼丁显著降低了R-(-)-氟卡胺的清除量，从395+/-121(S.D.)至335+/-88mlmin-1。这一变化可归因于代谢清除量的减少，伴随着氟卡胺两种主要代谢物的形成减少，在代谢不良的受试者中未观察到。R-(-)-氟卡胺的肾清除率显著升高。4.奎尼丁不改变S氟卡胺的清除量。5.氟卡胺治疗的药理作用(QRS增宽、心律失常抑制)略有增加，但不明显。6.在接受慢性氟卡胺治疗的广泛代谢物患者中，如果抑制P450IID6，将导致血浆浓度升高。
1. Recent reports have indicated a role for the P450IID6 polymorphism in the stereoselective disposition of single doses of the antiarrhythmic flecainide. 2. In this study, we evaluated the effects of adding low dose quinidine, a potent inhibitor of P450IID6, to chronic flecainide therapy in patients with arrhythmias. 3. In five extensive metabolizer patients, quinidine significantly reduced the clearance of R‐(‐)‐flecainide, from 395 +/‐ 121 (s.d.) to 335 +/‐ 88 ml min‐1. This change was attributable to a decrease in metabolic clearance, was accompanied by decreased formation of the two major metabolites of flecainide and was not observed in a poor metabolizer subject. The renal clearance of R‐(‐)‐flecainide rose significantly. 4. Quinidine did not alter the clearance of S‐(+)‐flecainide. 5. The pharmacologic effects of flecainide therapy (QRS widening, % arrhythmia suppression) were slightly, but not significantly, increased. 6. In extensive metabolizer patients receiving chronic flecainide, increased plasma concentrations will develop if P450IID6 is inhibited.