Document Detail


Droperidol and ondansetron in vitro electrophysiological drug interaction study.
MedLine Citation:
PMID:  19678851     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Droperidol and ondansetron are potent anti-emetic agents which are often administered together. Although both drugs prolong QT interval in man by inhibition of Human Ether-a-go-go Related Gene-coded potassium channels, only droperidol was tested using more integrated experimental models. Therefore, we studied the effects of both compounds and their combination on action potentials (AP) of rabbit Purkinje fibers using conventional intracellular glass microelectrode. Purkinje fibers, driven at 1 Hz, were exposed to increasing concentrations (from 0.001 to 10 microm) of droperidol (n = 7) or ondansetron (n = 8) at 30 min intervals at 36.5 degrees C. Other fibers were exposed to a constant droperidol concentration (0.1 microm) alone (n = 7) or together with the same increasing concentrations of ondansetron (n = 6). Droperidol increased AP duration measured at 90% repolarization (APD90) in a concentration-dependent manner from 4.4 +/- 0.8% (mean +/- SEM) after 1 nm to a maximum of 158 +/- 72% after 1 microm. Ondansetron significantly increased APD90 by 5.3 +/- 2.1% at 100 nm up to 76 +/- 14% after 10 microm. Early after-depolarization occurred in 6/7 fibers exposed to droperidol and 1/8 fibers exposed to ondansetron. When given together, pure additive effects were observed. The concentrations that increased APD90 by 50% were 0.25 +/- 0.25 microm droperidol, 3.8 +/- 2.4 microm ondansetron and 1.5 +/- 0.8 microm ondansetron when given together with droperidol. Both ondansetron and droperidol prolong AP duration in Purkinje fibers, droperidol being 10 times more potent than ondansetron. Combination of ondansetron and droperidol exhibits an additive effect on AP duration. However, within clinically relevant concentrations, ondansetron does not further increase the AP prolongation caused by droperidol alone.
Authors:
Jacques Weissenburger; Christian Funck-Brentano; Patrice Jaillon; Beny Charbit
Publication Detail:
Type:  In Vitro; Journal Article     Date:  2009-08-12
Journal Detail:
Title:  Fundamental & clinical pharmacology     Volume:  23     ISSN:  1472-8206     ISO Abbreviation:  Fundam Clin Pharmacol     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-17     Completed Date:  2010-02-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8710411     Medline TA:  Fundam Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  719-26     Citation Subset:  IM    
Affiliation:
Universit?? Pierre et Marie Curie, Service de Pharmacologie, Paris, France. jacques.weissenburger@upmc.fr
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects*
Animals
Antiemetics / pharmacology*
Droperidol / pharmacology*
Drug Combinations
Drug Interactions
Electrophysiology
Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
Female
Male
Ondansetron / pharmacology*
Purkinje Fibers / drug effects*,  physiology
Rabbits
Chemical
Reg. No./Substance:
0/Antiemetics; 0/Drug Combinations; 0/Ether-A-Go-Go Potassium Channels; 548-73-2/Droperidol; 99614-02-5/Ondansetron

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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