Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration

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.