Preliminary investigation of the safe dose of oleandrin when administered orally to Beagles

OBJECTIVE The purpose of the study reported herein was to determine the dose of oleander extract and oleandrin (the key pharmacologically active constituent) that could be safely administered PO to dogs. ANIMALS 42 purebred Beagle dogs were used to study an extract of Nerium oleander . METHODS 3 studies were performed in 42 purebred young adult (ages 12 months or older) Beagle dogs using a supercritical fluid extract of N oleander leaves. The first study was an 8 -day initial dose -ranging study in 2 dogs, a second 7 -day repeat -dosing study was performed in 4 dogs, and the final study was performed in 32 dogs where test subjects were given extract or placebo once daily for 28 consecutive days via oral (gavage) administration followed by a 14day recovery period. RESULTS At 2.3 mu g/kg of oleandrin, there were no observable adverse effects during the duration of the study. Adverse effects were not seen until doses exceeded 6.9 mu g/kg of oleandrin, at which time mild, reversible clinical signs were noted. However, a dose > 460 mu g of oleandrin/kg was fatal in 1 of 2 dogs in this study. CLINICAL RELEVANCE The studies reported here, taken in totality, suggest that doses exceeding 6.9 mu g/kg of oleandrin may be associated with cardiac abnormalities. An estimated no treatment effective adverse event oral dose of oleandrin appears to be 4.6 mu g of oleandrin/kg. Higher doses may be tolerable but should be used with appropriate monitoring.