Influence of footshock stress on pharmacokinetics of nicorandil in rats.

The influence of footshock stress on the pharmacokinetics of nicorandil was examined in rats. In the group exposed to a 30-min period of footshock immediately after the oral administration of nicorandil (10 mg/kg), plasma nicorandil levels were markedly lower than those in the control group 30-120 min after administration. Plasma levels after the subcutaneous injection of nicorandil (5 mg/kg) were also slightly but significantly lower in stressed rats than in control rats. When footshock was applied from 60 min after oral administration or 30 min after subcutaneous injection (the time when the plasma nicorandil level was maximum), it also significantly decreased the plasma levels thereafter. Furthermore, footshock applied immediately after intravenous injection of nicorandil (3 mg/kg) significantly decreased the plasma levels 30-60 min after injection. Plasma levels of N-(2-hydroxyethyl) nicotinamide, one of the main metabolites of nicorandil, were slightly increased 30 min after the intravenous injection of nicorandil (10 mg/kg) by footshock. Nicorandil levels in the heart, kidney, and skin were significantly lower in the stressed rats similar to the change in the plasma level, but levels in the muscle, liver, and thymus showed no significant difference. The urinary excretion of nicorandil tended to be higher in the stressed rats. These results suggest that footshock stress affects not only the absorption of nicorandil but also its distribution, metabolism, and excretion.