title: Pharmacokinetics and milk distribution characteristics of orbifloxacin following intravenous and intramuscular injection in lactating ewes.
abstract: 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 (Cl(B)) was 0.32 +/- 0.12 L/h x kg. Following i.m. administration, the maximum plasma concentration (C(max)) of 1.53 +/- 0.34 microg/mL was reached at t(max) 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 AUC(milk)/AUC(plasma) 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.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
authors.forename: A
authors.initials: A
authors.lastname: Goudah
authors.forename: H-J
authors.initials: HJ
authors.lastname: Cho
authors.forename: H-C
authors.initials: HC
authors.lastname: Shin
authors.forename: J-H
authors.initials: JH
authors.lastname: Shim
authors.forename: N L
authors.initials: NL
authors.lastname: Regmi
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
authors.forename: A M
authors.initials: AM
authors.lastname: Abd El-Aty
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D007262:Infusions, Intravenous / Q000662:veterinary; D007273:Injections, Intramuscular / Q000662:veterinary; D007711:Klebsiella pneumoniae / Q000187:drug effects; D007774:Lactation; D008892:Milk / Q000378:metabolism*; D012756:Sheep / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin; C095163:orbifloxacin