薬理と治療

Abstract

Objectives An open－label, dose escalation study was conducted to evaluate the safety, efficacy and pharmacokinetics of a single dose intravenous administration of Sigmart（nicorandil） in patients with acute heart failure or acute exacerbation of chronic heart failure. Methods Sigmart was administered intravenously at doses of 4 mg, 8 mg, 12 mg or 18 mg in 31 patients. Efficacy and safety parameters were measured for 3 hours in the 4 to 12 mg groups and 1 hour in the 18 mg group. Results In the“global improvement rate”assessment, the percentage of“improved”or better was 62.5％ at 12 mg and 100％ at 18 mg. Pulmonary artery wedge pressure（PAWP） decreased by over 20％ and cardiac index increased by over 10％ 5 to 15 minutes after administration of 12 and 18 mg of Sigmart. There was a significant correlation between plasma nicorandil concentration and PAWP decrease after the administration of Sigmart. There was no dose－proportionality in“safety rating”. Adverse reactions were reported in 2 patients, while both of them were mild and recovered without any treatment. Diastolic blood pressure decreased significantly 5（－15.9％）and 15 minutes（－9.3％）after the administration of 18 mg of Sigmart. Conclusions These results suggest that Sigmart can be safely administered and improves hemodynamics in patients with acute heart failure or acute exacerbation of chronic heart failure. In addition, the clinical optimal bolus dose of Sigmart is thought to be 12 mg.