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Tytuł:
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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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Autorzy:
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Goto A; Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Sakamoto K; Ina Research Inc., 2148-188 Nishiminowa, Ina-shi, Nagano, 399-4501, Japan.
Hagiwara-Nagasawa M; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Kambayashi R; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Chiba K; Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Nunoi Y; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Izumi-Nakaseko H; Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Matsumoto A; Department of Aging Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
Sugiyama A; Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Department of Aging Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan. Electronic address: .
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Źródło:
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Journal of pharmacological sciences [J Pharmacol Sci] 2020 Apr; Vol. 142 (4), pp. 172-175. Date of Electronic Publication: 2020 Jan 07.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Kyoto, Japan : Japanese Pharmacological Society, c2003-
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MeSH Terms:
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Atrioventricular Block*
Disease Models, Animal*
Drug Synergism*
Ketoconazole/*adverse effects
Terfenadine/*adverse effects
Torsades de Pointes/*chemically induced
Animals ; Chronic Disease ; Ketoconazole/administration & dosage ; Macaca fascicularis ; Polypharmacy ; Terfenadine/administration & dosage
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Contributed Indexing:
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Keywords: Cynomolgus monkey; Drug interaction; Torsade de pointes
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Substance Nomenclature:
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7BA5G9Y06Q (Terfenadine)
R9400W927I (Ketoconazole)
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Entry Date(s):
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Date Created: 20200127 Date Completed: 20200810 Latest Revision: 20200810
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Update Code:
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20240104
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DOI:
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10.1016/j.jphs.2019.12.007
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PMID:
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31982331
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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.
(Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
