Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders
Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders
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DOI：
10.1161/01.cir.102.16.1883
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发表时间：
2000-10-17
期刊：
影响因子：
37.8
通讯作者：
Turgeon, J
中科院分区：
文献类型：
--
作者：
Drolet, B;Rousseau, G;Turgeon, J
背景-已经报道了几例使用多潘立酮导致QT间期延长和室性快速性心律失常的病例，多潘立酮是一种胃动力和止吐药，在世界范围内都有，但在美国仍在研究中。虽然电解质紊乱，如低钾血症可以解释这些事件中的一些，我们假设，多潘立酮可能有意想不到的电生理效应诱发一些患者proarrhythmia.Methods和Results-Studies进行了9个离体豚鼠心脏，这表明反向使用依赖性延长心脏复极100 nmol/L多潘立酮。多潘立酮组动作电位时程较基线增加27%（从114+/-3到145+/-2 ms），增长了9%在周期长度为150 ms的起搏下观察到的最大心率（从97+/-2至106+/-3 ms）。证明了延迟整流钾电流的快速成分（I-Kr）的浓度依赖性阻滞。162 nmol/L多潘立酮使尾电流下降50%.Conclusions多潘立酮具有与西沙必利和III类抗心律失常药物相似的心脏电生理效应。在药物的临床相关浓度下观察到这些效应。因此，多潘立酮不应被视为西沙必利的无风险替代品，西沙必利是一种最近从美国市场撤回的药物。
Background-Several cases of QT prolongation and ventricular tachyarrhythmia have been reported with domperidone, a gastrokinetic and antiemetic agent available worldwide but still under investigation in the United States. Although electrolyte disturbances such as hypokalemia could account for some of these events, we hypothesized that domperidone may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia.Methods and Results-Studies were undertaken in 9 isolated guinea pig hearts, which demonstrated reverse use-dependent prolongation of cardiac repolarization by 100 nmol/L domperidone. Action potential duration increased 27% from baseline with domperidone (from 114+/-3 to 145+/-2 ms) during pacing at a cycle length of 250 ms, and a 9% increase (from 97+/-2 to 106+/-3 ms) was seen with pacing at a cycle length of 150 ms. Experiments in human ether-a-go-related gene (HERG)-transfected Chinese hamster ovary cells (n=32) demonstrated a concentration-dependent block of the rapid component (I-Kr) of the delayed rectifier potassium current. The tail current decreased by 50% at 162 nmol/L domperidone.Conclusions-Domperidone possesses cardiac electrophysiological effects similar to those of cisapride and class III antiarrhythmic drugs. These effects are observed at clinically relevant concentrations of the drug. Therefore, domperidone should not be considered a no-risk alternative to cisapride, a drug that was recently withdrawn from the US market.