Meropenem synovial fluid concentrations after intravenous regional limb perfusion in standing horses

To determine meropenem concentrations in radiocarpal (RC) joint fluid and plasma after intravenous regional limb perfusion (IVRLP).

In vivo experimental study.

Nine healthy adult mares.

Meropenem (500 mg) was injected in the forelimb of standing sedated horses via IVRLP with a pneumatic tourniquet inflated to 400 mmHg. Synovial fluid was collected from RC joints at 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours after meropenem injection. Blood samples were collected from the jugular vein at the same time points and at 5 and 15 minutes following injection. Meropenem concentrations were determined by using a microbiological bioassay.

Median synovial fluid concentrations reached a time of maximum synovial fluid concentration 0.5 hours after IVRLP. Synovial fluid concentrations varied greatly, with a mean maximum synovial fluid concentration of 25.6 µg/mL (range, below limit of quantitation to 75.5). Concentrations remained above the breakpoint for susceptibility (1 µg/mL) for 3 hours (last nonzero concentration measured, median) and 4.1 hours (predicted, mean). Concentrations >6 µg/mL were measured for 2 hours (observed, median) and 1.7 hours (predicted, mean). Six horses had mild swelling at the injection site.

Administration of 500 mg meropenem resulted in highly variable concentrations between horses and achieved levels above clinically relevant minimum inhibitory concentration for a minor portion of a once-daily dosing interval.

If time-dependent pharmacodynamics apply, IVRLP with 500 mg of meropenem may be ineffective and would likely promote resistance.