Ultrastructural Localization of Nicorandil in the Heart of Rats

To examine the intracellular localization of nicorandil in the heart, [14C]nicorandil and [3H]nicorandil (3 mg kg(-1)) were given orally to rats. The maximum concentration (Cmax) of nicorandil in the myocardium was reached 15 min after the oral dosing. At this time subcellular localization of nicorandil was examined. Nicorandil and its denitrated metabolite, SG-86 were found in mitochondrial fractions and in cytosolic and microsomal fractions of the heart. Electron-microscopic autoradiograms recorded 15min after oral dosing of 3 mg kg(-1) [3H]nicorandil to rats also showed the presence of silver grains generated by the radioactive nicorandil or its metabolites in the mitochondria of the heart. We conclude that nicorandil given orally to rats is distributed in mitochondria of the heart.