Determinant of the distribution volume at steady state for novel quinolone pazufloxacin in rats

The distribution properties of the novel quinolone pazufloxacin (PZFX) in rats were compared with those of sparfloxacin (SPFX) and ofloxacin (OFLX). Following intravenous administration of these quinolones to rats, the distribution volume at steady state (Vd(ss)) of PZFX was found to be 0.945 L kg(-1), whereas for OFLX and SPFX it was 1.83 and 3.42 L kg(-1), respectively. In order to understand this difference in Vd(ss), first the contribution of each tissue to the Vd(ss) using pharmacokinetic parameters was estimated and it was found that the type of tissue contributing the most was muscle. Subsequently, we determined the extent of tissue binding and uptake clearance (CLuptake) in the muscle. The ratio of unbound fraction of plasma to unbound fraction of muscle was almost equal for all quinolones tested, with values of 1.60, 1.52 and 1.32 for PZFX, OFLX and SPFX, respectively. In contrast, the tissue CLuptake of PZFX in the muscle (0.012 mL min(-1) g(-1)) was significantly lower than that of OFLX and SPFX (0.118 and 0.195 mL min(-1) g(-1), respectively). These results suggest that the low Vd(ss) value for PZFX can be attributed to the low CLuptake in the muscle.