薬理と治療

Abstract

Objectives A placebo－controlled, single－blinded, dose escalation study was conducted to evaluate the safety, tolerability and pharmacokinetics when high doses of Sigmart（nicorandil） were administered intravenously to healthy male volunteers. Methods Sigmart was administered intravenously at either doses of 6 mg（stepⅠ）, 12 mg （stepⅡ）, 18 mg（step Ⅲ）, and 24 mg（step Ⅳ）or placebo at all 4 steps to nine subjects. One dosage, either Sigmart of placebo, was administered at every step to the same subjects. Results Adverse events caused by Sigmart were reported in 2 of 6 subjects in stepⅠ, 4 of 5 subjects in stepⅡ, 4 of 5 subjects in step Ⅲ, and 3 of 5 subjects in step Ⅳ. The most common events were headache, dull headache and nausea, which were all mild. A transientdecrease of blood pressure, and subsequent tachycardia, were observed in all treatment groups. These reactions were considered to be based upon the vasodilating action of Sigmart. Plasma concentration of nicorandil increased dependently upon the dosage of Sigmart. There was no marked difference in T1/2 among the groups. Non－linearity of pharmacokinetic parameters suggests that the elimination process of nicorandil might be saturated. In addition, a large variance in plasma concentration changes was observed between subjects.Conclusions These data demonstrated that single dose intravenous administration of Sigmart up to 24 mg was safe and well tolerated in healthy volunteer.