TY - JOUR T1 - Metabolic Disposition of the New Fluoroquinolone Antibacterial Agent DW116 in Rats JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1101 LP - 1103 VL - 25 IS - 9 AU - Y. H. Park AU - B. H. Jung AU - B. C. Chung AU - J. Park AU - C. Mitoma Y1 - 1997/09/01 UR - http://dmd.aspetjournals.org/content/25/9/1101.abstract N2 - The metabolic disposition of the new fluoroquinolone antibacterial agent DW116 has been studied in Sprague-Dawley rats. The compound was absorbed well and demonstrated excellent oral bioavailability. The plasma kinetic profiles were characterized by monoexponential elimination with an elimination half life of 3-4 hr. The apparent mean total clearance (ClT) and the volume of distribution (Vss) ranged from 221 ± 55 to 274 ± 27 ml/hr/kg and 1.0±0.1 to 1.5±0.2 l/kg, respectively, and were independent of dose between 4 and 20 mg/kg levels. The renal (ClR) clearance was 64.5 ml/hr/kg and the biliary (ClB) clearance was 33.8 ml/hr/kg. The combined value accounted for approximately one-half of the total clearance, indicating that the remaining one-half of the administered dose was eliminated via hepatic clearance. The major metabolite excreted in the bile was identified as the glucuromide ester of parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound, 19F-NMR and LC-MS methods. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were 28.6 ± 2.7% and 36.4 ± 1.8% of the administered dose and the corresponding biliary recoveries were 14.4 ± 5.5% and 37.0 ± 7.6%, respectively. The mass balance study after a single (100mg/kg) oral administration of 14C-DW116 indicated complete recovery of radioactivity over a 7-day period, accounting for approximately 60-70% in feces and 30-40% in urine.14C-DW116 extensively distributed during a prolonged process into all tissues with a rather slower penetration into the brain, lung, and muscle. The compound also readily crossed the placenta and was transferred to the fetus. The American Society for Pharmacology and Experimental Therapeutics ER -