PHARMACOKINETICS AND TOLERANCE OF WEEKLY OXYGENT(TM) CA INFUSIONS IN THE DOG

This study determined the OXYGENT(TM) CA (90% w/v perflubron emulsion, Alliance Pharmaceutical Corporation) dose necessary to achieve a 3 - 4% fluorocrit, and the tolerance of this dose administered once per week for four weeks to dogs. This study simulated OXYGENT(TM) CA use as a radiosensitizing agent. Six adult dogs were administered 6 ml/kg OXYGENT(TM) CA once per week for 4 weeks. Blood samples were collected following infusion, until fluorocrits were less than or equal to 0.5%. One week after the fourth infusion, three dogs were necropsied. Liver biopsies were obtained from the remaining three dogs which were monitored 12 additional weeks. All dogs achieved fluorocrits > 3.0% (3.5 - 5.1%) with the 6 ml/kg dose. A 3 ml/kg dose did not provide a fluorocrit > 3.0%. Serum bilirubin concentrations were elevated at 24-hour sampling times and declined within 72 hours. Elevations in ALT, SAP, and bile acids were noted. Splenic and hepatic microvasculature fibrosis occurred in the long-term study dogs. Thrombocytopenia occurred in 5/6 dogs, necessitating exclusion of one dog from 2 infusions. However, 3/5 thrombocytopenic dogs had titers for Ehrlichia. sp., which elicits thrombocytopenia. Therefore, we cannot conclude the effect of OXYGENT(TM) CA on platelets.