Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of orbifloxacin in Korean Hanwoo cattle

Abstract

The pharmacokinetics and pharmacodynamics of orbifloxacin were studied in six clinically healthy Hanwoo cows after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 3 mg/kg. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution and clearance of orbifloxacin after i.v. administration were 0.92 L/kg and 0.24 L/h x kg, respectively. Following i.m. administration, a slow and complete absorption with absolute bioavailability of 101.4%, and a maximum concentration (C(max)) of 1.17 microg/mL at 1.04 h were observed. The in vitro serum protein binding was 14.76%. The in vitro antibacterial activity of orbifloxacin against a pathogenic strain of Mannheimia haemolytica (M. haemolytica), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was determined. The ex vivo activity of orbifloxacin against M. haemolytica strain was also determined, and these data were integrated with the ex vivo bacterial counts to establish AUC(24h)/MIC values producing bacteriostatic action, bactericidal action and elimination of bacteria. Mean values were 32.7, 51.6 and 102.6 h, respectively. From these data, we predict that orbifloxacin, when administered i.m. at a dosage of 2.5-5 mg/kg once a day, would be effective against bovine pathogens, such as M. haemolytica. Additional studies may be needed to confirm its efficacy in a clinical setting, and to evaluate the penetration of the drug in diseased tissues.

Integration of Pharmacokinetic and Pharmacodynamic Indices of Orbifloxacin in Beagle Dogs after a Single Intravenous and Intramuscular Administration

“…The i.v. terminal half-life of orbifloxacin for this study was longer than those reported for goats (1.84 h), rabbits (2.5 h), sheep (3.16 h), and cows (3.2 h) (7,17,11,18) but is lower than those reported for horses (5.08 h) and camels (5.74 h) (6,11). The longer terminal half-life (7.1 h) after oral administration of orbifloxacin in dogs (14) compared to that for our study may be due to the different route of administration, analytical method (microbiological assay), or commercial preparation used in the study.…”

“…The excitation and emission wavelengths used with the fluorescence detector were 287 nm and 470 nm, respectively. Treatment of samples and validation of the chromatographic method through the determination of specificity, linearity, accuracy, precision, detection, and quantitation limits were similar to those of our reported method (7). The retention time for orbifloxacin was 6.5 min.…”

“…Similar values of i.m. bioavailability for orbifloxacin were reported in goats (105.01%), rabbits (109.87%), camels (97.47%), Korean Hanwoo cows (101.4%), and sheep (114%) (7,10,11,17,18). However, Davis et al (6) respectively), which indicates that absorption does not seem to affect the elimination of orbifloxacin in dogs.…”

“…From different animal studies, the protein binding of orbifloxacin is estimated to be 20% (6,7,10). Therefore, the free/ unbound fraction of orbifloxacin (fu) would be 0.8.…”

“…The pharmacokinetics (PK) of orbifloxacin have been evaluated in goats (17), in horses (6,12), in pigs (19), in rabbits (18), in dogs (14,15,20), in cats (20), in camels (10), in cattle (7), and recently, in sheep (11). The in vitro activity and clinical efficacy of orbifloxacin against naturally occurring bacterial infections of the skin and soft tissues in dogs have also been evaluated by different researchers (8,9,16,20,25).…”