Veterinary session

Enrofloxacin is a concentration-dependent bactericidal antibacterial agent, which belongs to the fluoroquinolone group. It has a broad antibacterial spectrum, effective against both Gram-positive and Gram-negative bacteria. It is absorbed well subcutaneously, intramuscularly and orally, has excellent tissue distribution and is able to cross the special barriers of the body due to its lipophilicity. The primary objective of our study was to determine the pharmacokinetic parameters of enrofloxacin in pig plasma and synovial fluid at the approved dose of 7.5 mg/kg, administered subcutaneously in a single dose, and to evaluate the relevance of the data in the treatment of arthritis caused by Glaesserella parasuis.

The experiment was performed on ten 10-week-old DanBred pigs, weighing 29.51± 1.71 kg, by collecting blood and synovial fluid samples before and after drug administration: blood samples were collected after 15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24 and 48 hours, and synovial fluid samples were collected after 1, 2, 3, 4, 8, 12, 24 and 48 hours.

Drug concentrations in the two fluid compartments were determined by liquid chromatography-mass spectrometry (LC-MS/MS). The resulting data were evaluated by concentration-time curves for blood plasma and synovial fluid, and then the significant pharmacokinetic parameters (tmax, Cmax, Cl, Vd, AUC0-∞, t1/2, Ke) were calculated by non-compartmental pharmacokinetic analysis.

The maximum concentration (Cmax) of enrofloxacin in plasma was reached in 5.03 ± 1.62 h (tmax), with a value of 1.66 ± 0.33 µg/ml. In the synovial fluid, it reached a Cmax of 1.67 ± 0.49 µg/ml in 8.60 ± 2.09 h. The clearance (Cl) of enrofloxacin in plasma was 0.19 ± 0.02 (l/h)/kg and in synovial fluid 0.18 ± 0.05 (l/h)/kg. The volume of distribution (Vd) was found to be 3.57 ± 0.64 l/kg in the former space and 2.96 ± 0.97 l/kg in the latter. The area under the curve (AUC0-∞) was 38.89 ± 3.89 (h × µg)/ml for plasma and 45.26 ± 12.68 (h × µg)/ml for synovial fluid.

Based on literature data, the recommended pharmacokinetic/pharmacodynamic limit (PK/PDCO) for septicaemia and arthritis caused by G. parasuis in healthy pigs is 1 µg/ml, assuming the AUC/MIC pharmacodynamic target value (28.64 hours), with a 90% probability of target attainment (PTA). In the case of the target pharmacodynamic value (43.12 hours) established in pigs infected with G. parasuis, the proposed PK/PD limit for septicaemia and arthritis caused by G. parasuis is 0.5 µg/ml, with a probability of 90%.