Perflubron Emulsion (Oxygent™):
A Temporary Intravenous Oxygen Carrier

Background

Perfluorocarbon (PFC) emulsions, first developed almost 40 years ago, possess physical properties that make them ideal temporary intravenous oxygen carriers for a variety of clinical indications where tissues may be at risk of hypoxia. The first commercial development of an injectable PFC emulsion occurred over 25 years ago when the Green Cross Corporation (Osaka, Japan) produced Fluosol, a 20 % w/v PFC emulsion emulsified primarily with Pluronic F-68, a synthetic poloxamer. In 1989, Fluosol became the only synthetic oxygen carrier approved by the FDA for use as an adjunct to high-risk coronary balloon angioplasty. Some limitations of this first generation product, however, included the need for frozen storage of the stem emulsion, the need to thaw and subsequently mix with annex solutions prior to use, and short product stability (8 hours) after reconstitution.

Over the past 10 years, Alliance Pharmaceutical Corp. (San Diego) has been developing Oxygent™, an improved second-generation PFC emulsion based on perflubron (perfluorooctyl bromide; C8F17Br). This concentrated 60 % w/v perflubron-based formulation is emulsified with lecithin as the only surfactant, has a median particle diameter of ∼ 0.17 µm, and can be stored for ∼ 2 years with standard refrigeration. Perflubron emulsion is presently in late-stage clinical testing as a temporary intravenous oxygen carrier in surgical patients, and is being developed in conjunction with Baxter Healthcare Corporation.

References

• 1 Keipert P E. Perfluorochemical Emulsions - Future Alternatives to Transfusion. Chang TMS (ed) In: Blood Substitutes: Principles, Methods, Products and Clinical Trials. Karger Landes Systems, Basel 1998: 127-156
• 2 Faithfull N S. Oxygen delivery from fluorocarbon emulsions - aspects of convective and diffusive transport.  Biomat Artif Cells Immob Biotech. 1992;  20 797-804
• 3 Habler O P, Kleen M S, Hutter J W. et al . Hemodilution and intravenous perflubron emulsion as an alternative to blood transfusion: effects on tissue oxygenation during profound hemodilution in anesthetized dogs.  Transfusion. 1998;  38 145-155
• 4 Habler O, Kleen M, Hutter J. et al . IV perflubron emulsion versus autologous transfusion in severe normovolemic anemia: effects on left ventricular perfusion and function.  Res Exper Med. 1998;  197 301-318
• 5 del Balzo U, Kornbrust E S, Strnat C A. et al . Hemostasis, hemodynamic and cardiac effects of cardiopulmonary bypass with perflubron emulsion.  J Invest Med. 1996;  44 415 A
• 6 Holman W L, Spruell R D, Ferguson E R. et al . Tissue oxygenation with graded dissolved oxygen delivery during cardiopulmonary bypass.  J Thorac Cardiovasc Surg. 1995;  110 774-785
• 7 Spiess B D, Braverman B, Woronowicz A W. et al . Protection from cerebral air emboli with perfluorocarbons in rabbits.  Stroke. 1986;  17 1146-1149
• 8 Guo J, White J A, Batjer H H. Intravenous perflubron emulsion administration improves the recovery of auditory evoked potentials after temporary brain stem ischemia in dogs.  Neurosurg. 1995;  36 350-357
• 9 Leese P T, Noveck R J, Shorr J S, Woods C, Flaim K E, Keipert P E. Randomized safety studies of intravenous perflubron emulsion. I: Effects on coagulation function in healthy volunteers.  Anesth Analg. 2000;  91 (4) 804-811
• 10 Noveck R J, Shannon E J, Leese P T. et al . Randomized safety studies of intravenous perflubron emulsion. II: Effects on immune function in healthy volunteers.  Anesth Analg. 2000;  91 (4) 812-822
• 11 Wahr J A, Trouwborst A, Spence R K. et al . A pilot study of the effects of perflubron emulsion, AF0104, on mixed venous oxygen tension in anesthetized surgical patients.  Anesth Analg. 1996;  82 103-107
• 12 Spahn D R, von Brempt R, Theilmeier G. et al . Perflubron emulsion delays blood transfusions in orthopedic surgery.  Anesthesiology. 1999;  91 1195-1208
• 13 Albahrani M J, Hill S E, Leone B J. et al . Use of perflubron emulsion (Oxygent™) enables augmented harvesting of autologous blood and reduces allogeneic blood transfusion: A Phase 2 study in cardiac surgery.  Anesth Analg. 2001;  92 (4 S) 2
• 14 Spahn D, Waschke K, Standl T. et al . and the Oxygent Study Group. Oxygent™ reduces allogeneic blood transfusions in noncardiac surgery: A Phase 3 study.  Eur J Anaesth. 2001;  18 (S 21) 58