Acute effects of increasing doses of nicorandil on renal function in man.
The effects of nicorandil, a nicotinamide derived vasodilator combining nitrate and potassium channel opener actions, on kidney function have not been determined. This study investigated changes in renal blood flow and glomerular filtration rate as estimated using simultaneous 131I-iodohippurate and 125I-iothalamate plasma clearances. Forty-two healthy subjects in sodium balance received placebo and 2.5 mg (n = 8), 5 mg (n = 9), 10 mg (n = 8), 20 mg (n = 8) or 30 mg (n = 9) nicorandil orally. Peak nicorandil plasma concentrations occurred in the first hour. Nicorandil produced dose related decreases in blood pressure with maximum reductions (mean +/- standard error of the mean) after 30 mg of -6 +/- 1 mmHg systolic and -8 +/- 2 mmHg diastolic. Renal blood flow averaged 655 +/- 28 ml/minute/1.73 m2 after placebo. Renal blood flow changed 10 +/- 11% after 2.5 mg, -6 +/- 8% after 5 mg, -12 +/- 11% after 10 mg, -11 +/- 5% after 20 mg, and 8 +/- 6% after 30 mg, however, these changes did not reach statistical significance. Glomerular filtration rate averaged 113 +/- 3 ml/minute/1.73 m2 and was unaltered after nicorandil. Nicorandil had no effect on filtration fraction but fractional excretion of sodium tended to decrease with dose. These dose-related effects of nicorandil are consistent with other mixed vasodilators. At therapeutic doses, renal perfusion and function are preserved despite reductions in systemic blood pressure by nicorandil.
Wolf
D L
DL
Upjohn Research Clinics, Upjohn Company, Kalamazoo, Michigan 49001.
Jungbluth
G L
GL
Metzler
C M
CM
Froeschke
M O
MO
DeLoof
M J
MJ
Luderer
J R
JR
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D007465:Iodohippuric Acid / Q000032:analysis; D007483:Iothalamic Acid / Q000032:analysis; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D020108:Nicorandil; D012079:Renal Circulation / Q000187:drug effects*; D016037:Single-Blind Method; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D004573:Electrolytes; D007457:Iodine Radioisotopes; D014665:Vasodilator Agents; D007465:Iodohippuric Acid; D007483:Iothalamic Acid; D009536:Niacinamide; D020108:Nicorandil