Pharmacokinetic and tissue analyses of levofloxacin in sheep (Ovis aries Linnaeus) after multiple-dose administration

The aim of this study was to assess the pharmacokinetic profile of LFX in sheep after intravenous (IV) and oral (PO) administration of 2 mg/kg LFX once a day for 5 days and to evaluate its tissue depletion in the muscles, heart, liver, lungs, and kidneys. Twenty healthy female sheep were randomly divided into two equal groups. Each group was further randomly subdivided into two equal subgroups (n = 5). Group 1 was used for blood collection and underwent a crossover design (2 x 2 Latin square). Group 2 was randomly subdivided into two equal subgroups (rt = 5) for IV and PO route respectively, and used for tissue collection. A single sheep was sacrificed at each time point and the organs were harvested. Samples were analyzed using a validated HPLC method with fluorescence detection. LFX administered orally was rapidly absorbed with a peak plasma concentration of 2866 +/- 239 ng/mL and an absolute oral bioavailability of 114 +/- 27.7%. The pharmacokinetic estimates were comparable between PO and IV administration. According to the pharmacokinetic/pharmacodynamic surrogate index (area under the curve / minimum inhibitory concentration) of 100-125, LFX has the potential to be an effective treatment for infections caused by bacteria with a MIC of 0.049-0.061 mu g/mL. LFX was detected for up to 48 h in all the tissues samples. The kidney had the highest LFX concentration after IV and PO administration. The AUC(tissue/plasma) ratio was lower than 1 in all tissues indicating absence of LFX tissue accumulation.