Limitation of complement activation by perfluorocarbon emulsions: superiority of lecithin-emulsified preparations.
A considerable body of evidence suggests that complement and granulocyte activation may be important in the occasional adverse reactions which occur on the administration of perfluorocarbon emulsions to patients. In an attempt to develop an emulsion which was less prone to activate complement than was the first product clinically tested, we devised an in-vitro protocol for the testing of an emulsion's ability to activate complement: emulsions were serially diluted, and were incubated with minimally-heparinized plasmas from each of several donors; the generation of C3a was assessed by commercial immunoassay. In such a system, F-Adamantane emulsions prepared with highly-purified lecithin as the emulsifier were consistently less complement-activating than comparable emulsions prepared with Pluronic F-68 as the emulsifier. Emulsification technique seemed unimportant, and HPLC fractionation of the Pluronics identified no innocuous subfraction. Application of these findings to an animal model is underway, to see if the superiority of lecithin-based emulsions is also evident in vivo.
Hammerschmidt
D E
DE
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Vercellotti
G M
GM
D000218:Adamantane; D001802:Blood Substitutes; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a; D004338:Drug Combinations / Q000009:adverse effects; D004655:Emulsions; D005079:Excipients; D005466:Fluorocarbons / Q000009:adverse effects / Q000494:pharmacology*; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines; D011060:Poloxalene / Q000009:adverse effects
D001802:Blood Substitutes; D003176:Complement C3; D004338:Drug Combinations; D004655:Emulsions; D005079:Excipients; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D010713:Phosphatidylcholines; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D015926:Complement C3a; D011060:Poloxalene; D000218:Adamantane