Add time:08/26/2019         Source:sciencedirect.com

The kinetic disposition of nicorandil, N-[2-(nitroxy)ethyl]-3-pyridinecarboxamide (I), 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 ± 0.11 h; Vdarea, 0.67 ± 0.04 L/kg; and total plasma clearance, 13.50 ± 1.05 mL/min/kg. After oral administration, nicorandil was rapidly absorbed (tmax, 0.58 ± 0.11 h). The oral bioavailability was calculated as 0.72 ± 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 ± 0.25 and 3.69 ± 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.

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