Efficacy of a single oral dose of isosorbide 5-mononitrate in normal dogs and in dogs with congestive heart failure

Isosorbide 5-mononitrate (5-ISMN) was evaluated in normal dogs and dogs wit h congestive heart failure (CMF) in a randomized, blinded, and placebo-cont rolled study. Equilibrium blood pool imaging was used to detect changes in regional blood volume distribution. Six normal dogs were administered place bo, 2, 3, and 4 mg/kg 5-ISMN PO on separate days with a 1-week washout peri od between randomized dosings. Six dogs with CHF were administered placebo or 4 mg/kg 5-ISMN on separate days with a 1-week washout period between ran domized dosings. I)ata were collected at baseline and at 15. 30. 45, 60. 90 . 120. 150. 180, 210, and 240 minutes after dosing. Measured variables incl uded indirect arterial blood pressure (BP). bean rate (HR). packed cell vol ume (PCV), scintigraphic count rates for normal dogs, and scintigraphic cou nt rates for CHF dogs. Blood for plasma 5-ISMN concentration determination was collected at 60 minutes. Scintigraphic counts were corrected for decay and expressed as a percentage of the whole. No differences were detected in BP HR. PCV, thoracic blood volume percentage (TBVP). or abdominal blood vo lume percentage (ABVP) between placebo and 5-ISMN in normal dogs at any dos e. No differences were detected in TBVP or ABVP between placebo and 5-ISMN in dogs with CHE Plasma 5-ISMN concentration exceeded the minimum therapeut ic concentration in all dogs and at all doses 60 minutes after drug adminis tration. Equilibrium blood pool imaging failed to detect a shift in blood v olume with oral 5-ISMN administration at any dose tested in normal dogs and dogs with CHE despite adequate drug absorption. On the basis of the result s of this study, 5-ISMN may not be beneficial in the treatment of dugs with CHF.