Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses.
OBJECTIVE
To measure serum polymyxin B concentration after single and repeated IV infusions in horses.


METHODS
5 healthy horses.


METHODS
In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios.


RESULTS
In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microg/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microg/mL and 1.91 +/- 0.50 microg/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microg/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration.


CONCLUSIONS
Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.
Morresey
Peter R
PR
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Mackay
Robert J
RJ
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006736:Horses / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D009500:Neutralization Tests / Q000662:veterinary*; D011112:Polymyxin B / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D011112:Polymyxin B