Randomized safety studies of intravenous perflubron emulsion. I. Effects on coagulation function in healthy volunteers

Previous perfluorocarbon (PFC) emulsions have been associated with transien t adverse events (i.e., platelet activation, decreased platelet count, febr ile responses, changes in hemodynamic function). The Phase I studies descri bed in this report were parallel, randomized, double-blinded, placebo-contr olled studies conducted in 48 healthy volunteers (n = 24 per study) with pe rflubron emulsion (Oxygent(TM); Alliance Pharmaceutical Corp., San Diego, C A). Because of the decreased platelet counts observed with previous PFC emu lsions and the intended use of perflubron emulsion in surgical patients, th ese studies assessed postdosing coagulation responses and hemostasis. PFC p harmacokinetic variables were also evaluated. The primary endpoint for exam ination of coagulation effects was prospectively defined as bleeding time. Subjects received either saline (3 mL/kg) control, or perflubron emulsion a t 1.2 g PFC/kg or 1.8 g PFC/kg, and were evaluated for a 14-day period. No postinfusion changes in bleeding time or differences in ex vivo agonist-ind uced platelet aggregation were observed. A 17% reduction in platelet count was observed 3 days after dosing in the 1.8-g PFC/kg group; levels recovere d to baseline by Day 7. The intravascular half-life of perflubron for the f irst 24 h was dose dependent: 9.4 +/- 2.2 h and 6.1 +/- 1.9 h in the 1.8- a nd 1.2-g PFC/kg groups, respectively. Results indicate that this perflubron emulsion did not affect coagulation function in healthy volunteers.