title: Intravenous anti-influenza drug oseltamivir will not induce torsade de pointes: Evidences from proarrhythmia model and action-potential assay.
abstract: We evaluated proarrhythmic risk of intravenous oseltamivir with chronic atrioventricular block canine model (n = 4) and action-potential assay on guinea-pig right ventricle (n = 5). Oseltamivir in doses of 3-30 mg/kg, i.v. did not induce torsade de pointes in the canine model, whereas that in concentrations of 30-300 μM decreased maximum rate of phase 0 depolarization, shortened action potential duration at 30%, 60% and 90% repolarization levels, but prolonged difference in action-potential duration between 30% and 90% repolarization levels in a concentration-related manner. These results indicate that oseltamivir will not induce torsade de pointes clinically, since it inhibits both inward and outward currents.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Hamaguchi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University, Tokyo 143-8540, Japan. Electronic address: atsushi.sugiyama@med.toho-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D054537:Atrioventricular Block; D001681:Biological Assay; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D053139:Oseltamivir / Q000494:pharmacology*; D016171:Torsades de Pointes
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir
keywords: Intravenous; Oseltamivir; Torsade de pointes