Lubna Nur Jaharat, Nakamura Yuji, Hagiwara-Nagasawa Mihoko, Goto Ai, Chiba Koki, Kitta Kumiko, Izumi-Nakaseko Hiroko, Ando Kentaro, Naito Atsuhiko T, Akie Yasuki, Sugiyama Atsushi
Department of Pharmacology, Toho University Graduate School of Medicine.
Department of Pharmacology, Faculty of Medicine, Toho University.
J Toxicol Sci. 2018;43(8):507-512. doi: 10.2131/jts.43.507.
We analyzed electropharmacological characteristics of microminipigs under halothane-anesthesia using anti-influenza virus drug oseltamivir, which has been known to possess multi-channel blocking properties, including Na, Ca and K channels (n = 4). Oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously infused over 10 min with an interval of 20 min, which provided peak plasma concentrations 1.4, 7.4 and 125.5 µg/mL, respectively. The low dose did not alter any of the cardiovascular variables. The middle dose decreased the heart rate at 30 min after the start of the infusion. The high dose transiently returned the heart rate toward the baseline for 10-15 min, but decreased it for 20-60 min; decreased the mean blood pressure for 5-60 min; prolonged the PR interval for 10-60 min, and the QRS width for 10-20 min; but shortened the QT interval for 10-30 min, and the QTc for 5-60 min. Thus, oseltamivir can suppress the sinus automaticity, and atrioventricular nodal and intraventricular conduction; and decrease the mean blood pressure, extents of which were greater in microminipigs than in beagle dogs in our previous observation in spite of similar plasma concentrations, reflecting higher sensitivity of microminipigs for Na and Ca channel inhibition than that of beagle dogs. In contrast to beagle dogs, oseltamivir shortened the repolarization period in microminipigs, indicating that oseltamivir can more potently inhibit the inward currents than the outward ones in the hearts of microminipigs. This information may help improve utilizatione of microminipigs as a laboratory animal.
我们使用抗流感病毒药物奥司他韦分析了氟烷麻醉下小型微型猪的电药理学特性,已知该药物具有多通道阻断特性,包括钠、钙和钾通道(n = 4)。分别以0.3、3和30 mg/kg的剂量在10分钟内静脉输注奥司他韦,间隔20分钟,其峰值血浆浓度分别为1.4、7.4和125.5 µg/mL。低剂量未改变任何心血管变量。中剂量在输注开始后30分钟时降低了心率。高剂量使心率在10 - 15分钟内短暂恢复至基线,但在20 - 60分钟内降低;使平均血压在5 - 60分钟内降低;使PR间期延长10 - 60分钟,QRS宽度延长10 - 20分钟;但使QT间期缩短10 - 30分钟,QTc缩短5 - 60分钟。因此,奥司他韦可抑制窦性自律性、房室结和室内传导;并降低平均血压,尽管血浆浓度相似,但在我们之前的观察中,小型微型猪的这些作用程度比比格犬更大,这反映出小型微型猪对钠和钙通道抑制的敏感性高于比格犬。与比格犬不同,奥司他韦缩短了小型微型猪的复极期,表明奥司他韦在小型微型猪心脏中对内向电流的抑制作用比对外向电流更强。这些信息可能有助于提高小型微型猪作为实验动物的利用率。
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