The vascular toxicosis of
lonidamine (40 mg/h) or vehicle infusion was investigated in six dogs.
Vasculitis and
thrombosis were observed in veins infused with
lonidamine but not in veins infused with vehicle. This finding suggests that it may not be possible to use
lonidamine infusion to circumvent therapeutic limitations associated with the oral
lonidamine formulation currently used in patients. We also investigated the systemic toxicosis of
lonidamine (400 mg/m2; rapid intravenous bolus) or vehicle in six other dogs that developed systemic
acidosis (pH < or = 7.0) during whole body
hyperthermia (42 degrees C x 90 min). Gross and histologic haemorrhage was observed in all dogs; however, haemorrhagic lesions in acidotic dogs receiving
lonidamine + WBH were more severe than changes observed in acidotic dogs receiving vehicle + WBH. These observations confirm the results of in vitro studies which suggest that the combined effect of
lonidamine and
hyperthermia is enhanced under acidic conditions. Furthermore, these findings indicate that
acid-base status of patients receiving
lonidamine during WBH must be monitored carefully to avoid serious complications.