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 dist ribution kinetics of ciprofloxacin and ofloxacin in muscle- bone- and skin- tissues included in the isolated hindlimb of the rat. Experiments were carr ied out in the isolated perfused hindlimb of the rat, administering a singl e dose of 45, 450 or 900 mug of each quinolone as a bolus injection. Outflo w perfusate samples were collected for 20 min and drug levels were determin ed by an HPLC technique. The mean transit time (MTT) and the distribution v olume 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 mu g, 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 mug, respectively) . The distribution of ciprofloxacin and ofloxacin in the rat hindlimb appea rs to be a dose-dependent process, at least for the dose range considered i n this study. This might explain the high variability in the distribution c oefficients reported for these drugs in literature. Copyright (C) 2000 John Wiley & Sons, Ltd.