WHY THE NEWER PRODUCTS ARE BETTER
Rev Fr Transfus Hemobiol 1992 Dec;35(6):391-406
[Fluorocarbon emulsions as injectable oxygen carriers. Recent progress and perspectives].
[Article in French]
Riess JG
Laboratoire de Chimie Moleculaire, Unite de Recherche Associee au CNRS, Universite
de Nice.
Fluorocarbon emulsions are presently being developed to serve as injectable oxygen
carriers (so-called "blood substitutes"). In this approach oxygen is simply dissolved in the
liquid carrier and the amount of gas dissolved is proportional to its partial pressure.
Increasing the O2-delivering capacity is therefore achieved more easily by increasing the
oxygen content of the air breathed by the patient than by increasing the dose of
fluorocarbon administered. The absence of a chemical bond between the gas and its
carriers allows over 90% of the transported oxygen to be delivered. The fluorocarbon
droplets act as oxygen carriers , and also appear to facilitate its diffusion. Chemically and
biologically highly inert, fluorocarbons are excreted by exhalation without being
metabolized. The first generation of emulsions, exemplified by Fluosol has only limited
efficacy due to its low fluorocarbon content, low intravascular persistence and insufficient
stability. It has to be stored and distributed frozen, then reconstituted prior to use. Fluosol
has nevertheless been licensed by the Food and Drug Administration for use during high
risk PTCA. The second generation of injectable fluorocarbon emulsions, exemplified by
Oxygent is 4-5 times more concentrated and consequently more efficacious than Fluosol.
Considerably more stable, this emulsion can be stored for over one year at 5-8 degrees C
and is ready for use. The fluorocarbon used has a significantly shorter organ-retention
time. The applications of the present emulsions are still limited by their short intravascular
persistence, and are those for which prolonged efficacy is not required, which includes
perioperative hemodilution, ischemia, cardioplegia, reperfusion, sensitization of tumors to
radio- and chemotherapy, organ preservation and diagnosis. The efficacy of the new
emulsions has been established in various animal models. The mild side-effects observed
in Phase I clinical trials appear to result from a transient activation of the
monocyte/macrophage system and to be suppressed prophylactically by cyclooxygenase
inhibitors or corticosteroids. Research is presently oriented towards controlling
intravascular persistence better, increasing emulsion stability further, minimizing
side-effects and optimizing emulsion characteristics for specific indications. |
