PHARMACOKINETICS OF PERAZINYL)-1,4-DIHYDRO-4-OXOQUINOLONE-3-CARBOXYLIC ACID HYDROCHLORIDE (DW-116), A NEW QUINOLONE ANTIBIOTIC IN RATS

The objectives of this study were to characterize the pharmacokinetics of 1-5-fluoro-2-pyridyl) -6-fluoro-7-(4-methyl-1-piperazinyl)-1 ,4-di hydro-4-oxoquinolone-3-carboxylic acid hydrochloride (DW-116), a newly developed quinolone antibiotic, and to compare these kinetics with th ose of ciprofloxacin and rufloxacin, representative quinolone antibiot ics, in rats. Rats were subjected to surgery involving catheterization of the femoral vein and artery. DW-116 (4, 20, or 200 mg/kg), ciprofl oxacin (20 mg/kg), or rufloxacin (20 mg/kg) was administered either in travenously (iv) or orally. Blood samples were collected at various ti mes and subjected to an HPLC assay for the quinolones. Temporal profil es of plasma concentration after iv administrations of DW-116 at doses of 4, 20, and 200 mg/kg exhibited an apparent multiexponential declin e. In the three doses examined, systemic clearance and steady-state vo lume of distribution of DW-116, calculated by model-independent method s, were in the range 0.17 similar to 0.23 L/h/kg and 2.90 similar to 4 .44 L/kg, respectively. When DW-116 was given orally at doses of 4, 20 , or 200 mg/kg, the AUC values were neatly identical to those followin g iv administration, indicating an almost complete absorption (i.e., t he percent bioavailability was 90.0 for 4 mg/kg, 99.0 for 20 mg/kg, an d 98.3 for 200 mg/kg) in the dose range examined. The absorption of DW -116 appears to be extremely rapid because the mean residence time cal culated from the oral administration data was not significantly differ ent from that for the iv administration. At a dose of 20 mg/kg, the me an residence time for iv administered ciprofloxacin and rufloxacin was smaller than that of DW-116, indicating that DW-116 remains in the bo dy longer than the other quinolones. Absolute percent bioavailabilitie s of ciprofloxacin (69.9%) and rufloxacin (84.9%) were smaller than th at obtained for DW-116 (99.0%). Because it has been reported that the in vivo antibacterial activity of DW-116 is comparable or superior to that of rufloxacin and ciprofloxacin, despite the fact that the in vit ro activity is significantly lower, the pharmacokinetics of this antib iotic may be responsible, at least in part, for the enhanced in vivo a ntibacterial activity of DW-116.