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

Publication date: Available online 7 January 2020Source: Journal of Pharmacological SciencesAuthor(s): Ai Goto, Kengo Sakamoto, Mihoko Hagiwara-Nagasawa, Ryuichi Kambayashi, Koki Chiba, Yoshio Nunoi, Hiroko Izumi-Nakaseko, Akio Matsumoto, Atsushi SugiyamaAbstractIt 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.
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research