Influence of dose on the distribution kinetics of ciprofloxacin and ofloxacin in the isolated hindlimb of the rat.

The aim of this study was to determine whether the dose influences the distribution kinetics of ciprofloxacin and ofloxacin in muscle- bone- and skin-tissues included in the isolated hindlimb of the rat. Experiments were carried out in the isolated perfused hindlimb of the rat, administering a single dose of 45, 450 or 900 microg of each quinolone as a bolus injection. Outflow perfusate samples were collected for 20 min and drug levels were determined by an HPLC technique. The mean transit time (MTT) and the distribution volume of ciprofloxacin significantly increased with the dose injected (MTT=1.47+/-0.69, 8.74+/-0.27 and 9.52+/-2.95 min for 45, 450 and 900 microg, respectively). A similar situation was observed with ofloxacin, although the increase in these parameters was less pronounced (MTT=3.65+/-0.86, 7.92+/-2.03 and 8.32+/-1.70 min for 45, 450 and 900 microg, respectively). The distribution of ciprofloxacin and ofloxacin in the rat hindlimb appears to be a dose-dependent process, at least for the dose range considered in this study. This might explain the high variability in the distribution coefficients reported for these drugs in literature.