Evaluation of different PK/PD ratios of three enrofloxacin preparations on the clinical response of pneumonic calves

Abstract

Importance: Enrofloxacin preparations are available for administration daily or every 3 days. This study presents clinical evidence to define which preparation is adequate to treat clinical cases of bovine respiratory disease (BRD) in calves.

Objective: To correlate the pharmacokinetics/pharmacodynamics (PK/PD) ratios of three pharmaceutical preparations of enrofloxacin with their clinical efficacy in treating BRD.

Methods: The PK/PD ratios of three enrofloxacin preparations were determined in healthy calves. Then, 48 BRD-affected calves initially treated IV with 2.2 mg/kg of flunixin-meglumine, were randomly assigned to treatment with: enrofloxacin dihydrate-hydrochloride (enro-C) 10% water suspension daily (10 mg/kg subcutaneous for three to six days); enro-C with alginate (enro-C/Al), and reference enrofloxacin (enro-R), both intended for treatment every 72-h in two occasions (10 mg/kg).

Results: The highest maximum plasma concentration (Cmax)/minimum inhibitory concentration (MIC) ratio was obtained with enro-C and the highest area under the curve (AUC)_0-72/MIC ratio with enro-R, and enro-C/Al exhibited an AUC_0-72/MIC smaller, but Cmax/MIC higher than enro-R. Based on repeated statistical measurements, clinical progress revealed that the best outcomes were observed with enro-C (p < 0.05), and no statistical differences resulted by comparing enro-C/Al with enro-R.

Conclusions and relevance: If the priority in calves affected by BRD is to speed up their recovery, and despite the more significant amount enro-C injected, using of lower doses of enrofloxacin as in the long-acting preparations is unsustainable. This study demonstrates that the clinical efficacy of enrofloxacin in cattle is optimally linked to Cmax/MIC rather than to AUC/MIC, which occurs better when injecting enro-C.

Keywords: Calves; PK/PD-ratios; bovine-respiratory disease; clinical efficacy; enrofloxacin.

Fig. 1. FLIR images in which body temperature can be measured with a sensitivity of < 0.06°C.

Fig. 2. Log₁₀ versus time mean serum concentration of enro-C, enro-C/Al, and reference enrofloxacin (enro-R from Baytril Max; Elanco Animal Health) in calves after the S.C. injection of 10 mg/kg in all three cases. The injected volume was divided into equal parts on either side of the neck.

S.C., subcutaneous.

Fig. 3. The sum of means of clinical signs in time in calves with bovine respiratory complex disease (severity graded 3), and treated with one of the following preparations of enrofloxacin: as enro-C water suspension injected daily; enro-C in 1% alginate injected every 72 h, and enro-R, the reference Baytril Max (Elanco Animal Health) injected every 72 h. All doses were S.C. injected, dividing the 10 mg/kg dose by either side of the neck region. Three evolution gradings are marked as detailed in Table 1.

S.C., subcutaneous.