The role of ketoconazole in the QTc interval prolonging effects of H1-antihistamines in a guinea-pig model of arrhythmogenicity.
We have carried out experiments to re-evaluate the influence of ketoconazole (400 mg kg-1,p.o.) on the effects of ebastine, terfenadine and loratadine on the QTc interval in conscious guinea-pigs. Following a previously described protocol of oral drug administration, but using telemetric recording of the ECG, we have found that the prolongation of the QTc interval attributed to ebastine and terfenadine is in fact entirely due to ketoconazole, and that neither terfenadine, ebastine nor loratadine produce any additional effects on subsequent administration.
Gras
J
J
Research Centre Almirall Laboratories, Cardener, Barcelona, Spain.
Llenas
J
J
Palacios
J M
JM
Roberts
D J
DJ
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male
D000935:Antifungal Agents; D006634:Histamine H1 Antagonists; D007654:Ketoconazole