Electropharmacological Effects of Oseltamivir Assessed in the Halothane-Anesthetized in vivo Canine Model

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The present study was designed to precisely assess the cardiovascular effects of oseltamivir using halothane-anesthetized canine model. Oseltamivir in doses of 0.3, 3, and 30 mg/kg/10 min, i.v., (n=4) was additionally administered, in which clinically recommended daily p.o. dose is 150 mg/body/day. During sinus rhythm, the low dose increased cardiac output; the middle dose increased mean blood pressure besides cardiac output, intraatrial and intraventricular conduction time; and the high dose decreased cardiac output, mean blood pressure, heart rate and left ventricular contraction, whereas it increased preload and afterload, atrioventricular conduction time, and ventricular repolarization period. On ventricular pacing, the low dose hardly affected any of the electrophysiological variables. The middle dose prolonged ventricular repolarization period at a pacing cycle length of 300 ms, which was not observed at 400 ms. The high dose prolonged ventricular repolarization period at 300 ms, the extent of which was comparable to that induced at 400 ms. Thus, oseltamivir showed the negative chronotropic, inotropic, dromotropic and hypotensive effects in addition to the repolarization delay. Reverse frequency-dependent delay of repolarization was not observed, but frequency-dependent one was demonstrated, suggesting that oseltamivir may have less great potential of proarrhythmia leading to the onset of torsade de pointes.
日本不整脈学会の論文