APPLICATION OF MUSCLE MICRODIALYSIS TO EVALUATE THE CONCENTRATIONS OFTHE FLUOROQUINOLONES PAZUFLOXACIN AND OFLOXACIN IN THE TISSUE INTERSTITIAL FLUIDS OF RATS

Muscle microdialysis has been used to determine the unbound concentrat ions of the fluoroquinolones, pazufloxacin and ofloxacin, in tissue in terstitial fluids (C-isf,C-u) of rats under steady state conditions. C -isf,C-u was estimated from the concentration in dialysate and the in- vitro permeability rate constant by the extrapolation method based on the clearance concept. Paper disks were inserted under the abdominal s kin of rats, and the drug concentrations in the fluids penetrating int o the disks (C-disk) were measured and compared with C-isf,C-u. The C- isf,C-u of pazufloxacin and ofloxacin in muscle were close to their un bound concentrations in the venous plasma; these were 75.3% and 77.1%, respectively, of the total concentrations in plasma at the steady sta te. The C-disk of pazufloxacin and ofloxacin were also close to their C-isf,C-u. These results indicate that the unbound concentrations of t he fluoroquinolones in the tissue interstitial fluids were the same as those in the venous plasma. The disk insertion technique seems to be useful for evaluating drug concentrations in tissue interstitial fluid .