Clinical pharmacology of nicorandil in patients with congestive heart failure.
Nicorandil is a nicotinamide derivative with a potential role in human therapeutics because of its potent vasodilating properties. The pharmacokinetics of oral nicorandil administration and the relationships between plasma nicorandil concentration and hemodynamic responses were examined in 25 patients with moderate to severe congestive heart failure. The dose range from 10 to 60 mg was studied. Elimination half-life for this dose range was substantially longer than that previously reported in normal volunteers. Total area under the curve increased in a curvilinear fashion with progressive dose increments, indicating a disproportionate increase in systemically available drug at higher doses. Hemodynamic responses generally correlated well with plasma nicorandil concentration, with rapid loss of cardiovascular activity corresponding to the efficient clearance of nicorandil.
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Division of Cardiology, Ohio State University College of Medicine, Columbus 43210.
Jungbluth
G L
GL
Binkley
P F
PF
MacKichan
J J
JJ
Mohrland
J S
JS
Wolf
D L
DL
Leier
C V
CV
Bindley
P F
PF
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002319:Cardiovascular System / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020108:Nicorandil; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil