The pharmacokinetics and haemodynamic effects of continuous nicorandil infusion in healthy volunteers

Autor: J. J. Ferry, Daniel L. Wolf, M. O. Froeschke, A. E. Hearron, J. R. Luderer, Carl M. Metzler
Rok vydání: 1993
Předmět:
Zdroj: European Journal of Clinical Pharmacology. 45:437-443
ISSN: 1432-1041
0031-6970
DOI: 10.1007/bf00315515
Popis: We have studied the pharmacokinetics and haemodynamic effects of nicorandil after a 12-h infusion. Nicorandil is a mixed vasodilator combining the actions of a nitrate and a potassium channel opener. Nicorandil was infused for 12 h in 21 healthy volunteers at rates of 0.05, 0.10, and 0.20 microgram.kg-1.min-1 using a placebo controlled, crossover design. Systemic blood pressure, heart rate, electrocardiographic (ECG) intervals, and cardiac output (impedance cardiography) were measured supine and standing. Dose-related, steady-state plasma nicorandil concentrations occurred within 3 to 4 h. Nicorandil's pharmacokinetics were linear with dose. Four 0.20 microgram.kg-1.min-1 nicorandil infusions were terminated early primarily because of moderate or severe headaches. There were no safety concerns (ECG intervals, laboratory assays). Blood pressure fell versus placebo only in the standing position and heart rate increased slightly (not significant). That is, standing blood pressure in the 6 to 12 h interval fell from baseline 8.0*/6.8, 1.6/5.1, and 9.8*/7.9* mmHg (systolic/diastolic, * = P < 0.05 versus placebo) at 0.05, 0.10, and 0.20 micrograms.kg-1.min-1 respectively. Cardiac output increased slightly above placebo at lower doses. Haemodynamic changes correlated poorly with plasma nicorandil concentrations. Similar total doses were less well-tolerated when extended over 12 h. We saw no evidence of pharmacodynamic tolerance to nicorandil within 12 h.
Databáze: OpenAIRE
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