tetano
Editor, Senior Moderator
Cardiovasc Toxicol. 2013 Feb 19. [Epub ahead of print]
Cardiohemodynamic and Electrophysiological Effects of Anti-influenza Drug Oseltamivir In Vivo and In Vitro.
Kitahara K, Nakamura Y, Tsuneoka Y, Adachi-Akahane S, Tanaka H, Yamazaki H, Takahara A, Yamazaki J, Ikeda T, Sugiyama A.
Source
Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan.
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 (max) 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 (max) 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.
PMID:
23420508
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23420508
Cardiohemodynamic and Electrophysiological Effects of Anti-influenza Drug Oseltamivir In Vivo and In Vitro.
Kitahara K, Nakamura Y, Tsuneoka Y, Adachi-Akahane S, Tanaka H, Yamazaki H, Takahara A, Yamazaki J, Ikeda T, Sugiyama A.
Source
Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan.
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 (max) 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 (max) 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.
PMID:
23420508
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23420508