Abstract
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.
Footnotes
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Send reprint requests to: Dr. Jongsei Park, Korea Institute of Science and Technology, Doping Control Center, P.O. Box 131, Cheongryang, Seoul 130-650, Korea.
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Received June 3, 1996; accepted May 6, 1997.
- Abbreviations used are::
- DW116
- 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-l-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride
- HP
- Hewlett-Packard
- AUC
- area under the plasma concentration vs. time curve
- CLR
- renal clearance
- CLB
- biliary clearance
- CLT
- total clearance
- Vss
- volume at steady-state
- The American Society for Pharmacology and Experimental Therapeutics
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