Pharmacokinetics of enrofloxacin and danofloxacin in plasma, inflammatory exudate, and bronchial secretions of calves following subcutaneous administration

Enrofloxacin (2.5 mg/kg of body weight) and danofloxacin (1.25 mg/kg) were administered subcutaneously to ruminating calves (n = 8) fitted with subcut aneous tissue cages. Concentrations of enrofloxacin, its metabolite ciprofl oxacin, and danofloxacin in blood (plasma), tissue cage exudate (following intracaveal injection of 0.3 mi of 1% [vol/wt] carrageenan), and bronchial secretions were measured by high-performance liquid chromatography (HPLC) a nd microbiological assay (enrofloxacin plus ciprofloxacin and danofloxacin) . Mean maximum concentrations (C-max) +/- standard deviations of enrofloxac in (0.24 +/- 0.08 mu g/ml), ciprofloxacin (0.11 +/- 0.03 [total, 0.34 +/- 0 .10] mu g/ml), and danofloxacin (0.23 +/- 0.05 mu g/ml) were detected in th e plasma of calves by HPLC. The C-max were 0.49 +/- 0.17 mu g/ml (enrofloxa cin equivalents) and 0.24 +/- 0.03 mu g/ml (danofloxacin) when they were me asured by microbiological assay. Mean C-max in exudate (HPLC) were 0.18 +/- 0.07 mu g/ml (enrofloxacin), 0.10 +/- 0.04 mu g/ml (ciprofloxacin), 0.27 /- 0.09 mu g/ml (enrofloxacin plus ciprofloxacin), and 0.19 +/- 0.05 mu g/m l (danofloxacin), and concentrations in exudate exceeded those in plasma fr om 8 h (enrofloxacin and ciprofloxacin) or 6 h (danofloxacin) after drug ad ministration. The C-max were 0.34 +/- 0.09 mu g/ml (enrofloxacin equivalent s) and 0.22 +/- 0.04 mu g/ml (danofloxacin) in exudate when they were measu red by the microbiological assay. The maximum mean concentration achieved i n bronchial secretions (HPLC) were 0.07 +/- 0.04 mu g/ml (enrofloxacin), 0. 04 +/- 0.07 mu g/ml (ciprofloxacin), 0.10 +/- 0.05 mu g/ml (enrofloxacin pl us ciprofloxacin), and 0.12 +/- 0.09 mu g/ml (danofloxacin). The maximum me an concentration in bronchial secretions from a limited number of animals f rom which samples were available for microbiological assay were 0.27 +/- 0. 11 mu g/ml (n = 4 [enrofloxacin equivalents]) and 0.14 +/- 0.02 mu g/ml (n = 3 [danofloxacin]). With predictive models of efficacy (C-max/MIC and area under the concentration-time curve/MIC ratios in plasma) for Pasteurella m ultocida (MIC of enrofloxacin, 0.06 mu g/ml [24]; MIC of danofloxacin, 0.06 mu g/ml [6]), enrofloxacin produced scores of 8.17 and 52.00, respectively , compared to those of danofloxacin, which were 4.02 and 23.05, respectivel y. With the dosing rates recommended in some markets by manufacturers, enro floxacin and danofloxacin achieved concentrations above the MICs for import ant pathogenic organisms in plasma, tissue cage exudate, and bronchial secr etion. Since fluoroquinolones display concentration-dependent activities, C -max/MIC ratios may be critical to efficacy. In the United States enrofloxa cin is currently the only fluoroquinolone licensed for food animals and dos ages for acute respiratory disease are 2.5 to 5 mg/kg for 3 days or 7.5 to 12.5 mg/kg once. The higher dosages on a single occasion are likely to conf er C-max/MIC ratios that are associated with greater clinical efficacy.