الكاتب: Multiple References

The purpose of the current investigation is to elucidate the pharmacokinetic profiles of orbifloxacin (OBFX) in lactating ewes (n = 6) following intravenous (i.v.) and intramuscular (i.m.) administrations of 2.5 mg ⁄kg W. In a crossover study, frequent blood, milk, and urine samples were drawn for up to 48 h after the end of administration, and were then assayed to determine their respective drug concentrations through microbiological assay using Klebsiella pneumoniae as the test micro-organism. Plasma pharmacokinetic parameters were derived from plasma concentration–time data using a compartmental and noncompartmental analysis, and validated a relatively rapid elimination from the blood compartment, with a slope of the terminal phase of 0.21 ± 0.02 and 0.19 ± 0.06 per hour and a half-life of 3.16 ± 0.43 and 3.84 ± 0.59 h, for i.v. and i.m. dosing, respectively. OBFX was widely distributed with a volume of distribution V(d(ss)) of 1.31 ± 0.12 L ⁄kg, as suggested by the low percentage of protein binding (22.5%). The systemic body clearance (ClB) was 0.32 ± 0.12 L ⁄hÆkg. Following i.m. administration, the maximum plasma concentration (Cmax) of 1.53 ± 0.34 lg ⁄mL was reached at tmax 1.25 ± 0.21 h. The drug was completely absorbed after i.m. administration, with a bioavailability of 114.63 ± 11.39%. The kinetic milk AUCmilk ⁄AUCplasma ratio indicated a wide penetration of orbifloxacin from the bloodstream to the mammary gland. OBFX urine concentrations were higher than the concurrent plasma concentrations, and were detected up to 30 h postinjection by both routes. Taken together, these findings indicate that systemic administration of orbifloxacin could be efficacious against susceptible mammary and urinary pathogens in lactating ewes.