Ishizaki T, Chiba K, Suganuma T, Sasaki T, Kamiyama H, Nakano H
J Pharm Sci. 1984 Apr;73(4):494-8. doi: 10.1002/jps.2600730416.
The kinetic disposition of nicorandil, N-[2-( nitroxy )ethyl]-3- pyridinecarboxamide (1), and its main metabolic product, N-[2-(hydroxy)-ethyl]-3- pyridinecarboxamide (II), was studied after administering intravenous and oral doses (2.5 mg/kg) of nicorandil to the same beagle dogs. The plasma concentrations were measured using a high-performance liquid chromatographic method. The pharmacokinetic data derived from intravenous administration of nicorandil were: t1/2, 0.73 plus/minus 0.11 h; Vdarea , 0.67 plus/minus 0.04 L/kg; and total plasma clearance, 13.50 plus/minus 1.05 mL/min/kg. After oral administration, nicorandil was rapidly absorbed (tmax, 0.58 plus/minus 0.11 h). The oral bioavailability was calculated as 0.72 plus/minus 0.07. The metabolic formation of the corresponding alcohol after intravenous and oral administration of the parent compound appeared to occur quite efficiently, and its elimination half-life (3.09 plus/minus 0.25 and 3.69 plus/minus 0.88 h after intravenous and oral administration of nicorandil, respectively) was longer than that of the parent compound. Since the dose employed in this study was much higher than the expected therapeutic doses, whether such a good bioavailability after a lower dose of the drug would be obtained in humans remains unanswered.
在同一只比格犬静脉注射和口服（2.5mg/kg）尼可地尔后，研究了尼可地尔（N-[2-(硝氧基)乙基]-3-吡啶甲酰胺，(1)）及其主要代谢产物N-[2-(羟基)乙基]-3-吡啶甲酰胺（II）的动力学处置。采用高效液相色谱法测定血浆浓度。静脉注射尼可地尔获得的药代动力学数据为：t1/2，0.73±0.11小时；Vdarea，0.67±0.04L/kg；总血浆清除率，13.50±1.05mL/min/kg。口服后，尼可地尔迅速吸收（tmax，0.58±0.11小时）。口服生物利用度计算为0.72±0.07。静脉注射和口服母体化合物后相应醇的代谢形成似乎相当有效，其消除半衰期（分别在静脉注射和口服尼可地尔后为3.09±0.25和3.69±0.88小时）比母体化合物长。由于本研究中使用的剂量远高于预期治疗剂量，较低剂量药物在人体中是否能获得如此良好的生物利用度仍未可知。
