|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1991 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1990 : ¥1,500,000 (Direct Cost : ¥1,500,000)
In the present study, influences of emotinal stress on pharmacokinetics of various therapeutic drugs such as nicorandil, isosorbide dinitrate, vasodilators with nitrate, and tlieophylline, bronchodilator, were investigated in male Wistar rats. Restilts obtained were as follows ;
(A)Influence of footshock stress on pharmacokinetics of nicorandil --- In the group exposed to footshock(30 min)after the oral administration of nicorandil(10 mg/kg), plasma nicorandil levels were markedly lower than those in the control group. Plasma levels after the subcutaneous injection(5 mg/kg)were also slightly but significantly lower in stressed rats than in control rats. Furthermore, footshock applied immediately after intravenous injection of nicorandil(3 mg/kg)significantly decreased the plasma levels. Nicorandil levels in the heart, kidney, and skin were significantly lowel, in th e stressed rats, but levels in the muscle, liver and tliymus showed no difference. The urinary excretion of nicorandil ten
ded to be higher in the stressed rats. These results suggest that footshock stress affectsnot only tlie absorption of nicorandil but also its distribution, metabolism and excretion.
(B)Influence of footshock stress on Pharmacokinetics of isosorbide dinitrate--- The plasma level of isosorbide dinitrate intraperitoneally adiministered to rats stressed by footsliock was almost the same as that in the control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2- isosorbide mononitrate, were lower in stressed rats than in the control rats, suggestidg that footsliock stress may idfluence the metabolism and/or excretion of the metabolites.
(C)Influences of various emotional stresses on pharmacokinetics of theophylline--- In the group exposed to footsliock(30-60 min)after oral administration of theophylline(20 mg/kg), plasma theophylline levels were significantly lower than those in the control rats. Futhermore in the group immobilized by mesh wire(30-60 min)after the drug administration. the plasma levels were also markedly lower.
These results suggest that emotional stress such as footshock and immobilization afffects pliarmacokinetics of various therapeutic drugs such as nicorandil, isosorbide dinitrate and theophylline. Less