Efficacy of a Single Oral Dose of Isosorbide 5‐Mononitrate in Normal Dogs and in Dogs with Congestive Heart Failure

Abstract

Isosorbide 5‐mononitrate (5‐ISMN) was evaluated in normal dogs and dogs with congestive heart failure (CHF) in a randomized, blinded, and placebo‐controlled study. Equilibrium blood pool imaging was used to detect changes in regional blood volume distribution. Six normal dogs were administered placebo, 2, 3, and 4 mg/kg 5‐ISMN PO on separate days with a 1‐week washout period 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 randomized dosings. Data were collected at baseline and at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes after dosing. Measured variables included indirect arterial blood pressure (BP), heart rate (HR), packed cell volume (PCV), scintigraphic count rates for normal dogs, and scintigraphic count 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 volume percentage (ABVP) between placebo and 5‐ISMN in normal dogs at any dose. No differences were detected in TBVP or ABVP between placebo and 5‐ISMN in dogs with CHF. Plasma 5‐ISMN concentration exceeded the minimum therapeutic concentration in all dogs and at all doses 60 minutes after drug administration. Equilibrium blood pool imaging failed to detect a shift in blood volume with oral 5‐ISMN administration at any dose tested in normal dogs and dogs with CHF, despite adequate drug absorption. On the basis of the results of this study, 5‐ISMN may not be beneficial in the treatment of dogs with CHF.