Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses.
OBJECTIVE
To evaluate effects of polymyxin B sulfate (PMB) on response of horses to endotoxin, using an ex vivo model.


METHODS
8 healthy horses.


METHODS
In a crossover design, 3 doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and physiologic saline solution (control) were evaluated. Prior to and for 24 hours after administration of PMB, blood samples were collected into heparinized tubes for use in 2 assays. For the endotoxin-induced tumor necrosis factor (TNF) assay, blood samples were incubated (37 C for 4 h) with 1 ng of Escherichia coli or Salmonella Typhimurium endotoxin/ml of blood. Plasma was harvested and assayed. For the residual endotoxin activity assay, plasma was collected into sterile endotoxin-free borosilicate tubes, diluted 1:10 with pyrogen-free water, and incubated for 10 minutes at 70 C. Escherichia coli endotoxin (0.1 or 1 ng/ml of plasma) was added to the thawed samples prior to performing the limulus ameobocyte lysate assay. Serum creatinine concentrations were monitored for 1 week.


RESULTS
Compared with baseline values, PMB caused a significant dose- and time-dependent decrease in endotoxin-induced TNF activity. Compared with baseline values, residual endotoxin activity was significantly reduced after administration of 10,000 U of PMB/kg. Compared with baseline values, 1,000 and 5,000 U of PMB/kg should inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours, respectively. Serum creatinine concentrations remained within the reference range.


CONCLUSIONS
Results of the study suggest that PMB is a safe, effective inhibitor of endotoxin-induced inflammation in healthy horses.
Parviainen
A K
AK
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Barton
M H
MH
Norton
N N
NN
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D004731:Endotoxins; D004926:Escherichia coli; D006734:Horse Diseases / Q000097:blood / Q000188:drug therapy*; D006736:Horses; D011112:Polymyxin B / Q000494:pharmacology*; D012486:Salmonella typhimurium; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B