Open AccessHemodynamic, anti‐ischemic, and neurohumoral effects of slow‐release isosorbide‐5‐mononitrate in patients with coronary artery disease after short‐ and long‐term therapy
Author(s) -
Mitrovic V.,
Gessner C.,
Hain P.,
Müller K. D.,
Schlepper M.
Publication year - 1991
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.4960140307
Subject(s) - medicine , placebo , angina , isosorbide mononitrate , ejection fraction , coronary artery disease , isosorbide dinitrate , heart rate , cardiology , blood pressure , hemodynamics , anesthesia , heart failure , myocardial infarction , alternative medicine , pathology
In 20 patients with established coronary artery disease, stable angina pectoris and reproducible ST‐segment depression, the pharmacokinetics and pharmacodynamic effects of 60 mg slow‐release isosorbide‐5‐mononitrate (IS‐5‐MN) (10 patients) after a 7‐day therapy were compared with those of a placebo group (10 patients) using a randomized double‐blind, placebo‐controlled study design. Ten patients could be controlled after long‐term therapy over a mean of 399 ± 111 days. There was no significant change under IS‐5‐MN of either blood pressure, heart rate, rate–pressure product, or myocardial oxygen consumption. Treatment over one week significantly reduced ST‐segment depression 4 and 8 h after drug intake (38–48% of the placebo value, p<0.01). Maximum reduction in ST‐segment depression was found 4 and 8 h after IS‐5‐MN intake both after one‐week and long‐term therapy at the time of peak plasma drug concentration (341 ± 95 and 405 ± 125 ng/ml, respectively). At a residual plasma concentration below 100 ng/ml, ST depression was not significantly improved 24 h after drug intake compared with placebo. Technetium‐99m ventriculography showed an insignificant increase in ejection fraction and a slight reduction of ventricular volumes after both short‐ and long‐term therapy with IS‐5‐MN (p>0.05). The drug's plasma levels were higher under chronic than under short‐term therapy which may be due to enzyme saturation. Maximum IS‐5‐MN plasma concentrations at a mean of 445 ± 116 ng/ml were reached after 5.8 ± 2.9 h. Beta‐phase half‐life of elimination was 9 ± 3 h. IS‐5‐MN administered as a single 60 mg dose of a slow‐release preparation/day proved to have a favorable pharmacokinetic profile as well as an efficient anti‐ischemic activity after both short‐ and long‐term therapy. Problems of tolerance or activation of hormonal counter‐regulation due to vasodilation were not observed.