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In various parts of the world, many 10% enrofloxacin commercial preparations for water medication of chicken are being employed. To avoid the development of bacterial resistance to this agent, the original trademark and similar preparations must be bioequivalent. To assess whether or not bioequivalence exists among the pioneer vs. three commercial preparations of enrofloxacin, a controlled pharmacokinetic study was conducted. The following variables were compared: maximal plasma concentration (Cpeak), time to Cpeak, bioavailability (expressed as the area under the concentration vs. time curve), elimination half-life, and the shapes of the respective time-serum concentrations of enrofloxacin profiles. Results indicate that all three similar commercial preparations had lower Cpeak values than the reference formulation, being 39.62 to 67.77% of the corresponding Cpeak reference. Additionally, bioavailability of enrofloxacin in the pioneer product was statistically higher (P < 0.05). Based upon these results, we conclude that although all preparations were formulated as water-soluble products, bioequivalence studies are mandatory for the analogue formulations to ensure product comparability. Lack of product bioequivalence could facilitate the development of bacterial resistance and limit the useful life span of the product.

Pharmacokinetic parameters of fosfomycin in cattle were determined after administration of buffered disodium fosfomycin either intravenously (i.v.) or intramuscularly (i.m.) at a dose of 20 mg/kg/day for 3 days. Calculated concentrations at time zero and maximum serum concentrations were 34.42 and 10.18 mug/mL, respectively. The variables determined, the elimination half-life of the drug remained unchanged during the 3 days ( = 1.33 +/- 0.3 h for the i.v. route and = 2.17 +/- 0.4 h for the i.m. route). Apparent volumes of distribution suggest moderated distribution out of the central compartment (V(darea) = 673 mL +/- 27 mL/kg and V(dss) = 483 +/- 11 mL/kg). Bioavailability after i.m. administration was 74.52%. Considering fosfomycin as a time-dependent antibacterial drug, plasma concentration vs. time profiles obtained in this study, suggest that clinically effective plasma concentrations of fosfomycin could be obtained for up to 8 h following i.v. administration and approximately 10 h after i.m. injection of 20 mg/kg, for susceptible bacteria. In addition to residue studies in milk and edible tissues, a series of clinical assessments, using fosfomycin at 20 mg/kg b.i.d. or t.i.d. are warranted before this antibacterial drug should be considered for use in cattle.

No abstract

To define the impact that use of different levels of hard water has on the bioavailability of the antibacterial, enrofloxacin, in poultry, an oral bioavailability-pharmacokinetic study of the drug was carried out. Two hundred fifty clinically healthy broilers, divided into 5 groups, were individually dosed orally with 10 mg/kg of enrofloxacin diluted to 0.1%. The enrofloxacin was diluted with water of increasing hardness in accordance with an international grading system. After dosing, blood samples were obtained at predetermined times. Serum was recovered and quantified for enrofloxacin by means of an agar diffusion bacteriological method. The composite serum concentrations of enrofloxacin and metabolites vs. time relationships were analyzed using software for compartmental pharmacokinetics. Results show that there were statistically significant differences in the following pharmacokinetic variables: maximal serum concentrations (Csmax), area under the time vs. concentration curves, and half-lives of the elimination phases. The means of these values showed a linear decay of Csmax from one group to the next as water hardness increased. Chemical analysis of water calcium and magnesium ions revealed the formation of coordination groups. Lack of interference with the microbiological activity in vitro of enrofloxacin diluted in hard water indicated that diminished absorption may be partly responsible for reduction in bioavailability. These results stress the need for proper water supply when enrofloxacin is used and point out a factor that must be taken into account when clinical outcomes do not comply with expectations.