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.