Summary The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single‐dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (Vss= 1.17 ± 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 ± 0.042 l/kg.h, which is related to a long elimination half‐life (t1/2β= 4.74 ± 0.8 h and 5.47 ± 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 ± 14.2 min) and presented high bioavailability (F = 87.9 ± 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8‐fold (range 3–15) compared with pre‐injection levels, but this activity decreased to 3‐fold during the 24 h follow‐up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC ≥ 0.25 μg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most Gram‐negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration‐dependent effect and a long postantibiotic effect against Gram‐negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (Vss = 0.72 +/- 0.15 L/kg) lower than normal goats (Vss = 1.19 +/- 0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl) decreased from 0.24 +/- 0.12 L/kg/h in healthy animals to 0.13 +/- 0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC). Consequently, mean residence time (MRT) was also slightly increased in sick animals (MRT = 5.28 +/- 00.99 and 6.09 +/- 01.45 h, in healthy and febrile animals, respectively).

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This study compared pharmacokinetic profiles in cattle dosed subcutaneously with two different formulations of enrofloxacin (5% and 10%) at a dose of 5 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by a HPLC/u.v. method. The pharmacokinetic parameters of enrofloxacin and its metabolite were similar in both injectable formulations. Enrofloxacin peak plasma concentration (5%: 0.73 +/- 0.32; 10%: 0.60 +/- 0.14 microg/mL) was reached at 1.21 +/- 0.52 and 1.38 +/- 0.52 h to 5 and 10%, respectively. The terminal half-live and area under curve were 2.34 +/- 0.46 and 2.59 +/- 0.46 h, and 3.09 +/- 0.81 and 2.93 +/- 0.58 microg x h/mL, to 5 and 10%, respectively. The AUC/MIC(90) and Cmax/MIC(90) ratios for both formulations exceed the proposed threshold values for optimized efficacy and minimized resistance development whilst treating infections or septicaemia caused by P. multocida and E. coli.

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