Utilization of the chronic atrioventricular block cynomolgus monkey as an in vivo model to evaluate drug interaction-associated torsade de pointes.

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ID: 86808
2020
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Abstract
It has been difficult to experimentally reproduce synergistic effects of ketoconazole on terfenadine-induced torsade de pointes. We assessed proarrhythmic effects of terfenadine (30 mg/kg, p.o.) with/without ketoconazole (100 mg/kg, p.o.) pretreatment using the chronic atrioventricular block cynomolgus monkeys with repeated-measured design (n = 4). Terfenadine with ketoconazole pretreatment repeatedly induced non-sustained torsade de pointes in each animal, although terfenadine alone did not induce it at all. Thus, the chronic atrioventricular block cynomolgus monkeys can be used for studying drug interaction-associated torsade de pointes, providing a non-clinical strategy to circumvent untoward drug interactions in patients specially under polypharmacy.
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goto2020utilizationjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Goto, Ai;Sakamoto, Kengo;Hagiwara-Nagasawa, Mihoko;Kambayashi, Ryuichi;Chiba, Koki;Nunoi, Yoshio;Izumi-Nakaseko, Hiroko;Matsumoto, Akio;Sugiyama, Atsushi;
Journal Journal of pharmacological sciences
Year 2020
DOI
S1347-8613(19)35743-3
URL
Keywords
torsade de pointes cynomolgus monkey drug interaction

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