Pharmacokinetics of marbofloxacin administered via intravenous regional limb perfusion in dairy cows: evaluation of two different tourniquets

Abstract

ObjectivesThis study evaluated synovial and systemic plasma pharmacokinetic variables of marbofloxacin after a single intravenous regional limb perfusion (IVRLP) performed using two different tourniquets in clinically healthy, standing, non-sedated dairy cows. The authors hypothesised that the type of tourniquet used for IVRLP would influence the synovial fluid concentration of marbofloxacin in the perfused distal limb.DesignThe study had a randomised parallel-group design.MethodsTen adult dairy cows were included. Unilateral hindlimb IVRLP through the dorsal common digital III vein was performed in two groups of five cows (group 1: wide rubber tourniquet; group 2: manual pneumatic tourniquet) using 0.67 mg/kg of marbofloxacin. The tourniquet was applied proximal to the tarsus and maintained for 30 minutes. Samples of jugular blood and synovial fluid from the tibiotarsal joints of the perfused limb were obtained before and at intervals after IVRLP. All samples were analysed for drug concentrations using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were determined to establish the influence of tourniquet types. Differences were considered significant at P≤0.05.ResultsNo adverse effects from the procedure or marbofloxacin were observed in any animal. Significant differences in synovial concentrations and pharmacokinetic parameters were measured. The mean ± sd areas under the concentration versus time curve from time 0 to 24 hours were 178.98±58.08 µg hour/ml for group 2 and 21.11±9.93 µg hour/ml for group 1. The mean ± sd maximum marbofloxacin concentrations were 75.50±10.19 µg/ml for group 2 and 6.35±1.47 µg/ml for group 1.ConclusionsPerforming IVRLP using the dorsal common digital III vein and a manual pneumatic tourniquet set at 300 mmHg above the tarsus in standing cows resulted in significantly higher marbofloxacin concentrations in the tibiotarsal joint compared with those with the wide rubber tourniquet.Trial registrationLocal ethical committee (number 41/2012/CEISA).

Review of digital anatomy, infectious causes of lameness, and regional intravenous perfusion in cattle

“…114 Studies on RIVP in the bovine using cefazolin, ceftiofur sodium, florfenicol, tetracycline HCl, ampicillin-sulbactam, and marbofloxacin have shown that antimicrobial levels in venous blood and synovial fluid in joints distal to the tourniquet can reach concentrations well above the MIC for common bacterial pathogens associated with DDS as well as other infectious agents of the bovine foot. 26,34,52,54,91,118 Additionally, a single RIVP of either marbofloxacin or ceftiofur sodium has been reported to result in effective clinical treatment of interdigital phlegmon in dairy cattle. 154 However, a single regional perfusion of 1000 mg of tetracycline hydrochloride was unsuccessful in resolving digital dermatitis in dairy cows.…”

Regional Limb Perfusion

“…The pharmacokinetics of several antibiotics have been described when used as an RLP in cattle, including: tetracycline, cefazolin, ceftiofur, florfenicol, ampicillin, and marbofloxacin. 3,5,9,10,16,18 Selection of the right drug for regional perfusion in each case should be based on a number of factors. The intended spectrum of activity is of paramount importance, especially whether or not mycoplasma is expected or known to be present in the case at hand.…”

In vitro Elution of Penicillin, Ampicillin, Tetracycline, Tulathromycin, and Florfenicol From Plaster of Paris Beads

“…Regional perfusions can achieve antimicrobial concentrations many times higher than the MIC of common pathogens, however use is limited to the distal extremity due to the need to place a tourniquet proximal to the area of interest and because high concentrations of drug are generally not maintained for very long after tourniquet removal. Antibiotics reported for use in regional perfusions in cattle include florfenicol, ampicillin-sulbactam, marbofloxacin, and ceftiofur (16)(17)(18)(19). Constant rate infusion systems are also able to achieve high antimicrobial concentrations, however breakage or blockage of the intrasynovial catheter is common (15).…”