Pharmacokinetics of orbifloxacin and its concentration in body fluids and in endometrial tissues of mares

Pharmacokinetics and distribution of orbifloxacin into body fluids and endo metrium was studied in 6 mares after intragastric (IG) administration at a single dose rate of 7.5 mg/kg body weight. Orbifloxacin concentrations were serially measured in serum, synovial fluid, peritoneal fluid, urine, cereb rospinal fluid, and endometrial tissues over 24 hours. Minimum inhibitory c oncentrations of orbifloxacin were determined for 120 equine pathogens over an Ii-month period. The mean peak serum concentration (C-max) was 2.41 +/- 0.30 mug/mL at 1.5 hours after administration and decreased to 0.17 +/- 0. 01 mug/mL (C-min) at 24 hours. The mean elimination half-life (t(1/2)) was 9.06 +/- 1.33 hours and area under the serum concentration vs time curve (A UC) was 20.54 +/- 1.70 mg.h/L. Highest mean peritoneal fluid concentration was 2.15 +/- 0.49 mug/mL at 2 hours. Highest mean synovial fluid concentrat ion was 1.17 +/- 0.28 mug/mL at 4 hours. Highest mean urine concentration w as 536.67 +/- 244.79 mug/mL at 2 hours. Highest mean endometrial concentrat ion was 0.72 +/- 0.23 mug/g at 1.5 hours. Mean CSF concentration was 0.46 /- 0.55 mug/mL at 3 hours. The minimum inhibitory concentration of orbiflox acin required to inhibit 90% of isolates (MIC90) ranged from less than or e qual to 0.12 to > 8.0 mug/mL, with gram-negative organisms being more sensi tive than gram-positive organisms. Orbifloxacin was uniformly absorbed in t he 6 mares and was well distributed into body fluids and endometrial tissue . At a dosage of 7.5 mg/kg once a day, many gram-negative pathogens, such a s Actinobacillus equuli, Escherichia coli, Pasteurella spp., and Salmonella spp. would be expected to be susceptible to orbifloxacin.