Accumulation of enrofloxacin in canine peripheral leukocytes and its effect on the concentration of enrofloxacin at a site of inflammation

Enrofloxacin is a fluoroquinolone antimicrobial approved for use in veterinary medicine. Among its characteristics is the possibility that it accumulates in leukocytes. Infection is a major cause of inflammation. Leukocytes migrate to sites of inflammation as part of the host response to inflammation and may transport enrofloxacin to sites of inflammation. This study was divided in two phases: Phase one documented the accumulation of enrofloxacin by canine circulating leukocytes and Phase two demonstrated that white blood cells delivered enrofloxacin to a site of inflammation.; Enrofloxacin was administered orally to dogs at a single dose of 7.5, 10 and 20 mg/kg. Concentrations of enrofloxacin and its active metabolite ciprofloxacin, were measured in plasma, leukocytes and red blood cells until the drug was no longer detectable. Time course of drug disappearance was compared among doses and between leukocytes and plasma. Concentrations of both antimicrobials paralleled in plasma and in leukocytes, but concentrations in leukocytes were higher than in plasma. Accumulation in leukocytes reached 63-fold for enrofloxacin and 35-fold for ciprofloxacin.; To document that enrofloxacin accumulation in leukocytes results in an increase of drug at sites of inflammation (Phase two), dogs were surgically implanted with bilateral subcutaneous tissue chambers. Localized inflammation was induced in one chamber with a sterile irritant, while the other chamber served as a control. Peripheral leukocytes were collected from each dog, exposed in vitro to radiolabeled enrofloxacin, and injected back into the donor. Concentrations of radiolabeled enrofloxacin were measured in leukocytes and extracellular fluid collected from inflamed and non-inflamed tissue chambers, as well as from serum and circulating leukocytes. Enrofloxacin was not detected in serum, circulating leukocytes or in the non-inflamed chamber. Enrofloxacin was, however, detected in both extracellular fluid and leukocytes collected from the inflamed tissue chamber.