PHARMACOKINETICS OF LB20304, A NEW FLUOROQUINOLONE, IN RATS AND DOGS

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half- life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 9 3.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver micr osome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-26.6% for dogs, and 56.9-59.6% for huma ns. Its tissue concentration levels in liver, stomach, small intestine , and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligibl e in rats. The 48 hr urinary recovery of the dose was 44% for IV dosin g and 14% for oral dosing, whereas the 48 hr biliary recovery of the d ose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summar y, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribu tion.