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Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders.
Circulation. 2000 Oct 17; 102(16):1883-5.Circ

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 Therefore, domperidone should not be considered a no-risk alternative to cisapride, a drug that was recently withdrawn from the US market.

Authors+Show Affiliations

Institut de cardiologie de Québec, Hôpital Laval, Facultés de Pharmacie, Université Laval, Sainte-Foy, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11034933

Citation

Drolet, B, et al. "Domperidone Should Not Be Considered a No-risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders." Circulation, vol. 102, no. 16, 2000, pp. 1883-5.
Drolet B, Rousseau G, Daleau P, et al. Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders. Circulation. 2000;102(16):1883-5.
Drolet, B., Rousseau, G., Daleau, P., Cardinal, R., & Turgeon, J. (2000). Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders. Circulation, 102(16), 1883-5.
Drolet B, et al. Domperidone Should Not Be Considered a No-risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders. Circulation. 2000 Oct 17;102(16):1883-5. PubMed PMID: 11034933.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Domperidone should not be considered a no-risk alternative to cisapride in the treatment of gastrointestinal motility disorders. AU - Drolet,B, AU - Rousseau,G, AU - Daleau,P, AU - Cardinal,R, AU - Turgeon,J, PY - 2000/10/18/pubmed PY - 2001/2/28/medline PY - 2000/10/18/entrez SP - 1883 EP - 5 JF - Circulation JO - Circulation VL - 102 IS - 16 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/11034933/Domperidone_should_not_be_considered_a_no_risk_alternative_to_cisapride_in_the_treatment_of_gastrointestinal_motility_disorders_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.cir.102.16.1883?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -