Evaluation of the distribution of enrofloxacin by circulating leukocytes to sites of inflammation in dogs

Abstract

Objective - To determine the effect of WBC accumulation on the concentration of enrofloxacin in inflamed tissues in dogs. Animals - 6 adult Bloodhounds. Procedures - Dogs were instrumented bilaterally with tissue chambers. Peripheral WBCs collected from each dog were exposed in vitro to radiolabeled enrofloxacin (14C-ENR). Inflammation was induced with carrageenan in 1 chamber. Ten hours later, treated cells were administered IV to each dog such that 14C-ENR was delivered at a mean ± SD dosage of 212 ± 43 μg. Samples of extracellular fluid from inflammation and control chambers and circulating blood were then collected before (baseline) and for 24 hours after WBCs were administered. Samples were centrifuged to separate WBCs from plasma (blood) or chamber fluid. Radiolabeled enrofloxacin was scintigraphically detected and pharmacokinetically analyzed. Comparisons were made between extra- and intracellular chamber fluids by use of a Student paired t test. Results - 14C-ENR was not detectable in plasma, peripheral WBCs, control chambers, or baseline samples from inflammation chambers. However, 14C-ENR was detected in extracellular fluid from inflammation chambers (mean ± SD maximum concentration 2.3 ± 0.5 ng/mL) and WBCs (maximum concentration, 7.7 ± 1.9 ng/mL). Mean disappearance half-life of 14C-ENR from extracellular fluid and WBCs from inflammation chambers was 26 ± 10 hours and 17 ± 6 hours, respectively. Conclusions and Clinical Relevance - WBCs were responsible for the transport and release of 14C-ENR at sites of inflammation. Accumulation of drug by WBCs might increase the concentration of drug at the site of infection, thus facilitating therapeutic success.