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- Title
Cardiohemodynamic and Electrophysiological Effects of Anti-influenza Drug Oseltamivir In Vivo and In Vitro.
- Authors
Kitahara, Ken; Nakamura, Yuji; Tsuneoka, Yayoi; Adachi-Akahane, Satomi; Tanaka, Hikaru; Yamazaki, Hiroshi; Takahara, Akira; Yamazaki, Junichi; Ikeda, Takanori; Sugiyama, Atsushi
- Abstract
Electropharmacological effects of oseltamivir were studied in comparison with pilsicainide using halothane-anesthetized dogs ( n = 4) and isolated left atrium of guinea pigs ( n = 5). Oseltamivir (0.3, 3 and 30 mg/kg, i.v.) or pilsicainide (1 and 3 mg/kg, i.v.) was additionally administered to the dogs. The low dose of oseltamivir provided clinically relevant plasma concentrations with C of 4 μM. The low and middle doses of oseltamivir increased cardiac output, whereas the middle dose increased blood pressure and delayed intra-atrial conduction and ventricular repolarization. The high dose of oseltamivir exerted negative chronotropic, inotropic and hypotensive effects, while it delayed intra-atrial, atrioventricular nodal and intra-ventricular conduction and ventricular repolarization. Use-dependent delay of ventricular repolarization was observed after oseltamivir, whereas reverse use-dependent prolongation was induced by pilsicainide. Moreover, oseltamivir more selectively suppressed intra-atrial conduction than intra-ventricular conduction, which was less selective for pilsicainide. Action potential assay using isolated atrium indicated that oseltamivir (10 μM) decreased V more than pilsicainide (10 μM) and that oseltamivir (10-100 μM) prolonged action potential duration, which was not induced by pilsicainide (1-10 μM). Thus, oseltamivir in clinically relevant to its 10 times higher doses is relatively safe, whereas 10-100 times higher doses possess unique electrophysiological profile.
- Subjects
HEMODYNAMICS; ELECTROPHYSIOLOGY; OSELTAMIVIR; IN vitro studies; LIDOCAINE; COMPARATIVE studies; HALOTHANE; LABORATORY dogs; THERAPEUTICS
- Publication
Cardiovascular Toxicology, 2013, Vol 13, Issue 3, p234
- ISSN
1530-7905
- Publication type
Article
- DOI
10.1007/s12012-013-9202-6