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 Sigmart (nicorandil) was administered through the combination of a bolus injection followed by continuous infusion in healthy male volunteers. Methods Sigmart was administered intravenously at a dose of 12 mg over 5 minutes followed by continuous infusion at rates of 6 mg／hour（stepⅠ）, 9 mg／hour（step Ⅱ）and 12 mg／hour（step Ⅲ）or placebo was administered for 235 minutes in a total of 9 subjects, with 6 subjects receiving Sigmart and 3 subjects receiving placebo.Results Adverse events caused by Sigmart were recorded in 5 of 6 in step Ⅰ, 6 of 6 in step Ⅱ, and 4 of 4 in step Ⅲ. The most common events were headache, and dull headache. All events were mild to moderate, and recovered when continuous infusion finished. Sustained blood pressure reduction and subsequent reflex tachycardia were observed during the infusion, which were considered to be associated with the vasodilating effect of Sigmart. Plasma concentrations of nicorandil increased rapidly just after bolus injection, then decreased rapidly over 30 minutes, and remained stable or increased depending on infusion rate.Conclusions These data demonstrated that combined intravenous administrations of Sigmart were safe up to bolus injection of 12 mg and continuous infusion of 12 mg／hour. How ever, the next study with acute heart failure, should start from a 12 mg bolus and a low dose of continuous infusion, 3 mg／hour.