(Circulation. 2000;102:1883.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders
From the Institut de cardiologie de Québec, Hôpital Laval
(B.D., P.D., J.T.) et Facultés de Pharmacie (B.D., J.T.) et de
Médecine (P.D.), Université Laval, Sainte-Foy, Québec,
Canada, and the Centre de Recherche, Hôpital du Sacré-C
ur
de Montréal (G.R., R.C., J.T.), Département de Pharmacologie,
Faculté de Médecine (G.R., R.C., J.T.) et Faculté de
Pharmacie (J.T.), Université de Montréal, Montréal,
Québec, Canada.
Correspondence to Jacques Turgeon, PhD, Dean, Faculty of Pharmacy, University of Montreal, CP 6128 succursale Centre-ville, Montreal QC Canada H3C 3J7. E-mail jacques.turgeon{at}umontreal.ca
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 (IKr) 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 Therefore, domperidone should not be considered a no-risk alternative to cisapride, a drug that was recently withdrawn from the US market.
Key Words: arrhythmia • ion channels • torsade de pointes • electrophysiology • long-QT syndrome
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