Utilization of the chronic atrioventricular block cynomolgus monkey as an in vivo model to evaluate drug interaction-associated torsade de pointes
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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DOI：
10.1016/j.jphs.2019.12.007
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发表时间：
2020-04-01
影响因子：
3.5
通讯作者：
Sugiyama, Atsushi
中科院分区：
文献类型：
--
作者：
Goto, Ai;Sakamoto, Kengo;Sugiyama, Atsushi
酮康唑对特非那定诱导的关节扭转的协同效应很难在实验上重现。我们采用重复测量设计（n = 4），评估了特非那定（30 mg/kg, p.o.）与酮康唑（100 mg/kg, p.o.）预处理/不预处理对慢性房室传导阻滞食食猴的促心律失常作用（n = 4）。特非那定联合酮康唑预处理在每只动物中反复诱导非持续性髋部扭转，但单独使用特非那定完全不诱导。因此，慢性房室传导阻滞食蟹猴可用于研究药物相互作用相关的扭转点，为避免药物相互作用的不良患者提供非临床策略，特别是在多种药物治疗下。(C) 2020作者。由Elsevier B.V.代表日本药理学会制作和主办。
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. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.