Randomized safety studies of intravenous perflubron emulsion. I. Effects on coagulation function in healthy volunteers.
Previous perfluorocarbon (PFC) emulsions have been associated with transient adverse events (i.e., platelet activation, decreased platelet count, febrile responses, changes in hemodynamic function). The Phase I studies described in this report were parallel, randomized, double-blinded, placebo-controlled studies conducted in 48 healthy volunteers (n = 24 per study) with perflubron emulsion (Oxygent; Alliance Pharmaceutical Corp., San Diego, CA). Because of the decreased platelet counts observed with previous PFC emulsions and the intended use of perflubron emulsion in surgical patients, these studies assessed postdosing coagulation responses and hemostasis. PFC pharmacokinetic variables were also evaluated. The primary endpoint for examination of coagulation effects was prospectively defined as bleeding time. Subjects received either saline (3 mL/kg) control, or perflubron emulsion at 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-induced 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 recovered to baseline by Day 7. The intravascular half-life of perflubron for the first 24 h was dose dependent: 9.4+/-2.2 h and 6.1+/-1.9 h in the 1.8- and 1.2-g PFC/kg groups, respectively. Results indicate that this perflubron emulsion did not affect coagulation function in healthy volunteers.
Leese
P T
PT
Innovex Inc., Lenexa, Kansas, USA.
Noveck
R J
RJ
Shorr
J S
JS
Woods
C M
CM
Flaim
K E
KE
Keipert
P E
PE
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004655:Emulsions; D005260:Female; D005334:Fever / Q000139:chemically induced; D005466:Fluorocarbons / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D005500:Follow-Up Studies; D006207:Half-Life; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D006842:Hydrocarbons, Brominated; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D012449:Safety
D003287:Contrast Media; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D010919:Placebos; C003072:perflubron