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.

Randomized safety studies of intravenous perflubron emulsion. II. Effects on immune function in healthy volunteers.

Particle size distribution is a major determinant of particle clearance by the mononuclear phagocytic system and the potential for concomitant activation of resident macrophages. To test the safety of a second-generation perflubron-based emulsion (60% perfluorocarbon [PFC] wt/vol; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA]) with a small mean particle size, two parallel, randomized, double-blinded, placebo-controlled studies were conducted in 48 healthy volunteers (n = 24 per study). The study described herein focuses on safety concerning immune function. The primary endpoint was defined prospectively as delayed hypersensitivity skin test responses with lymphocyte proliferative responses to mitogenic stimulation providing a secondary measure for changes in cell-mediated immunity. Subjects received either perflubron emulsion IV (1.2 g PFC/kg or 1.8 g PFC/kg) or saline (3 mL/kg) control. Perflubron emulsion had no effect on delayed hypersensitivity skin reactions, lymphocyte proliferative potential, circulating immunoglobulins, complement activation, or plasma levels of the inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta. Perflubron emulsion was generally well tolerated, although there was a dose-dependent increase in minor flu-like symptoms in the perflubron treatment groups at 24 h after dosing. Increased serum levels of interleukin-6 were observed in those subjects exhibiting febrile responses. The clinical safety profile of perflubron emulsion supports its continued investigation as a temporary oxygen carrier in surgical patients to reduce exposure to allogeneic blood transfusion.

The safety and applications of acellular human dermal allograft in ophthalmic plastic and reconstructive surgery: a preliminary report.

PURPOSE: To describe the uses and determine the safety of a commercially available acellular dermal allograft in ophthalmic plastic and reconstructive surgery. The existing literature regarding current applications and results using acellular dermal allograft is reviewed. METHODS: The study design was a retrospective, noncomparative case series. Participants consisted of 63 consecutive patients undergoing ophthalmic plastic and reconstructive surgery using an acellular dermal matrix graft. The main intervention was placement of a dermal allograft. Outcome measures included the degree of clinical improvement and complications for each patient. RESULTS: We used AlloDerm (LifeCell Corporation, The Woodlands, TX, U.S.A.) as a posterior lamellar conjunctival spacer graft, a soft tissue interpositional graft, and an orbital implant wrapping material. Clinical improvement was noted in all cases. There were no complications attributable to the acellular dermal matrix material. CONCLUSIONS: We describe several novel ophthalmic plastic and reconstructive surgical applications using acellular dermal allograft tissue. This material may be used safely as a posterior lamellar conjunctival spacer graft, a soft tissue interpositional graft, and a wrapping material. Clinically, the allograft appears to be biocompatible, nontoxic, and nonallergenic in the orbit, eyelid, and midfacial tissues. Long-term data and studies comparing the efficacy of acellular dermal allograft with conventional materials are necessary.

Perflubron as a gastrointestinal MR imaging contrast agent in the pediatric population.

OBJECTIVE: To evaluate the safety and efficacy of orally administered perflubron for bowel recognition on MR imaging in a pediatric population. MATERIALS AND METHODS: A multicenter trial evaluated 39 pediatric subjects before and after ingestion of perflubron with T1-, proton-density, and T2-weighted sequences through the abdomen and/or pelvis. Post-contrast images were compared with pre-contrast images. Safety was evaluated through assessment of adverse events, clinical laboratory parameters, and vital signs. RESULTS: With regard to efficacy analysis, improvement in the percent of bowel darkened was observed for 85 % of the subjects on T1-weighted images and for 95 % of the subjects on proton-density and T2-weighted images. For images of the abdominal region, the percent of bowel darkened was improved for 90-92 % of the subjects across pulse sequences. Improvement rates for the images of the pelvic region ranged from 71 % to 100 %. For at least 75 % of the subjects, proton-density and T2-weighted images of the body and tail of the pancreas, left lobe of the liver, mesenteric fat, and pathological tissue were improved relative to predosing images. Twenty-three percent of the subjects experienced some adverse effects, most of which were minor and related to the digestive system. Clinical laboratory and vital sign evaluations revealed no trends associated with the administration of perflubron. CONCLUSION: Perflubron is a relatively safe and effective gastrointestinal MR contrast agent in the pediatric population.

Preclinical and clinical studies on lymph node imaging using perflubron emulsion.

A perflubron emulsion is being developed as a contrast agent to enhance lymph nodes on computed tomography (CT) images. The emulsion is administered by percutaneous injection into the drainage field of the lymph nodes to be imaged. A series of preclinical studies was conducted to investigate the efficacy of the perflubron emulsion for enhancement of lymph nodes on CT images. The effects of dose (0.10 to 0.50 mL), application of massage, and route of administration were investigated in healthy New Zealand white rabbits. Results of these studies demonstrated that doses as low as 0.15 mL were efficacious for consistent enhancement of axillary lymph nodes on CT images after subcutaneous injections in the forepaw. Application of massage to the injection site decreased the time for maximum nodal enhancement from approximately 7 days to 2 days postinjection. A pilot study conducted in 18 healthy, male volunteers indicated dose-related enhancement of axillary lymph nodes on CT images following subcutaneous injections of the emulsion in the hand. Other than mild, transient injection-site discomfort, no clinically significant side effects were observed. These data demonstrate that the perflubron emulsion is safe and can enhance axillary lymph nodes on CT images following injections in the hand.