Influences of psychological stress produced by intraspecies emotional communication on nicorandil plasma levels in rats.

Influences of emotional stress on nicorandil pharmacokinetics were studied in rats that received physical and psychological stimuli (referred to as 'sender' and 'responder' rats, respectively) using the communication box paradigm. Concerning pharmacokinetic, there was no marked difference in the Tmax, Ka, Kel, T1/2 and Vd between the sender rats and the nonstressed control rats when both of which were orally administered 10 mg/kg of nicorandil. But the Cmax and AUC were lower and clearance (Cl) was higher in the sender rats. In the responder rats, there was no difference in Tmax, Ka, Kel, and T1/2. But the Cmax and AUC were lower and the Vd was higher than those of the control rats. On the other hand, when nicorandil was administered in a dose of 5 mg/kg subcutaneously, Tmax and T1/2 in the sender rats did not differ from those of the controls, but the Cmax, Ka and AUC were lower, and the Kel, Vd and Cl were higher. Between the responder and control rats, significant differences were found in all parameters except for Vd, i.e., Cmax, Ka, T1/2 and AUC were lower than those of control rats, and the Tmax, Kel and Cl were higher than those of control rats. This indicates that pharmacokinetics of nicorandil when administered orally and subcutaneously were influenced not only by physical stress but also by psychological stress.