Pharmacokinetics of orbifloxacin and its concentration in body fluids and in endometrial tissues of mares.
Pharmacokinetics and distribution of orbifloxacin into body fluids and endometrium 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, cerebrospinal fluid, and endometrial tissues over 24 hours. Minimum inhibitory concentrations of orbifloxacin were determined for 120 equine pathogens over an 11-month period. The mean peak serum concentration (Cmax) was 2.41+/-0.30 microg/mL at 1.5 hours after administration and decreased to 0.17+/-0.01 microg/mL (Cmin) at 24 hours. The mean elimination half-life (t1/2) was 9.06+/-1.33 hours and area under the serum concentration vs time curve (AUC) was 20.54+/-1.70 mg h/L. Highest mean peritoneal fluid concentration was 2.15+/-0.49 microg/mL at 2 hours. Highest mean synovial fluid concentration was 1.17+/-0.28 microg/mL at 4 hours. Highest mean urine concentration was 536.67+/-244.79 microg/mL at 2 hours. Highest mean endometrial concentration was 0.72+/-0.23 microg/g at 1.5 hours. Mean CSF concentration was 0.46+/-0.55 microg/mL at 3 hours. The minimum inhibitory concentration of orbifloxacin required to inhibit 90% of isolates (MIC90) ranged from < or = 0.12 to > 8.0 microg/mL, with gram-negative organisms being more sensitive than gram-positive organisms. Orbifloxacin was uniformly absorbed in the 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 as Actinobacillus equuli, Escherichia coli, Pasteurella spp., and Salmonella spp. would be expected to be susceptible to orbifloxacin.
Haines
G R
GR
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0136, USA.
Brown
M P
MP
Gronwall
R R
RR
Merritt
K A
KA
Baltzley
L K
LK
D000818:Animals; D019540:Area Under Curve; D001202:Ascitic Fluid / Q000737:chemistry / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects*; D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism*; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007408:Intestinal Absorption; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
D002939:Ciprofloxacin; C095163:orbifloxacin