Comparative evaluation of a new formulation of isosorbide dinitrate oral spray and sublingual nitroglycerin tablets

Abstract

The magnitude and time course of the hemodynamic effect of a new formulation of an aqueous solution of isosorbide dinitrate (ISDN) spray were compared with those of sublingual nitroglycerin (NTG) tablets in 12 patients with chronic congestive heart failure. The patients received, in a random order, ISDN spray, 2.5 mg, or sublingual NTG, 0.8 mg. Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug. The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours. The hemodynamic variables measured were comparable at baseline. Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances. Only ISDN spray significantly increased cardiac output. The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p < 0.02). The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG. Thus, the onset of the hemodynamic effect of the new formulation of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG.