Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders
- 17 October 2000
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 102 (16), 1883-1885
- https://doi.org/10.1161/01.cir.102.16.1883
Abstract
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-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 Therefore, domperidone should not be considered a no-risk alternative to cisapride, a drug that was recently withdrawn from the US market.Keywords
This publication has 8 references indexed in Scilit:
- Droperidol Lengthens Cardiac Repolarization due to Block of the Rapid Component of the Delayed Rectifier Potassium CurrentJournal of Cardiovascular Electrophysiology, 1999
- Modulation of HERG potassium channel properties by external pHPflügers Archiv - European Journal of Physiology, 1999
- Domperidone: A Peripherally Acting Dopamine2-Receptor AntagonistAnnals of Pharmacotherapy, 1999
- Exploring the Hidden Danger of Noncardiac DrugsJournal of Cardiovascular Electrophysiology, 1998
- Properties of HERG Channels Stably Expressed in HEK 293 Cells Studied at Physiological TemperatureBiophysical Journal, 1998
- Cisapride-induced long QT intervalThe Journal of Pediatrics, 1996
- Cardiac Arrhythmias during Cytotoxic Chemotherapy: Role of DomperidoneHuman Toxicology, 1985
- On the pharmacokinetics of domperidone in animals and man IV. The pharmacokinetics of intravenous domperidone and its bioavailability in man following intramuscular, oral and rectal administrationEuropean Journal of Drug Metabolism and Pharmacokinetics, 1981