PT  - JOURNAL ARTICLE
AU  - Y. H. Park
AU  - B. H. Jung
AU  - B. C. Chung
AU  - J. Park
AU  - C. Mitoma
TI  - Metabolic Disposition of the New Fluoroquinolone Antibacterial Agent DW116 in Rats
DP  - 1997 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 1101--1103
VI  - 25
IP  - 9
4099  - http://dmd.aspetjournals.org/content/25/9/1101.short
4100  - http://dmd.aspetjournals.org/content/25/9/1101.full
SO  - Drug Metab Dispos1997 Sep 01; 25
AB  - 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