Muscle distribution of antimicrobial agents after a single intravenous administration to rats

Drug Metab Pharmacokinet. 2002;17(3):237-44. doi: 10.2133/dmpk.17.237.


The purpose of this study was to evaluate the distribution of three fluoroquinolones (pazufloxacin, ciprofloxacin and ofloxacin) and a beta-lactam, ceftazidime in the tissue interstitial and intracellular spaces after a single intravenous administration to rats based on muscle microdialysis. The unbound concentration in the tissue interstitial fluid (C(isf,u)) after administration was estimated from the concentration in the dialysate by muscle microdialysis, the in vitro permeability rate constant, and the previously reported effective dialysis coefficient. The C(isf,u)s of pazufloxacin, ciprofloxacin, ofloxacin and ceftazidime in the muscle were close to their unbound concentrations in the venous plasma. These results were consistent with ones previously obtained at steady state. Based on these results, the total concentration in the tissue interstitial fluid (C(isf)) was calculated from the ratio of plasma protein binding, the plasma concentration, and previously reported interstitial-to-plasma albumin ratio in muscle of rats. The calculated C(isf) was compared with the muscle concentration (C(m)) obtained using the homogenized tissue. The C(isf) of ceftazidime was higher than the C(m). The C(isf) of pazufloxacin was found to be almost equal to its C(m). The C(isf)s of ciprofloxacin and ofloxacin were lower than their C(m)s with the exception of the values at 5 min after administration. These results indicate that ceftazidime is mainly distributed in the interstitial space of the muscle, that pazufloxacin is distributed equally in both the interstitial space and the tissue cells, and that ciprofloxacin and ofloxacin are mainly distributed in the tissue cells rather than the interstitial space.