Effects of bacterial lipopolysaccharide on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats

Pharmacokinetic parameters of DA-7867 were compared after intravenous and oral administration at a dose of 10 mg/kg to control rats and rats pretreated with Klebsiella pneumoniae lipopolysaccharide (KPLPS). After intravenous administration of DA-7867 at a dose of 10 mg/kg to 10 rats, metabolism of DA-7867 was minimal; however, the urinary and gastrointestinal excretion of DA-7867 were approximately 85% of intravenous dose when collected for up to 14 days. After intravenous administration to rats pretreated with KPLPS, the AUC was significantly greater (14, 100 versus 9810 mug (.) min/ mL), and this could be due to significantly slower total body clearance (CL, 0.709 versus 1.02 mL/min/kg). The slower CL in the rats could be due to significantly smaller fecal excretion of DA-7867 for up to 14 days (41.1 versus 58.8% of intravenous dose of DA-7867) because urinary excretion of DA-7867 was not significantly different between two groups of rats. After oral administration, the AUC values were not significantly different between two groups of rats and this was mainly due to decrease in absorption from the gastrointestinal tract in rats pretreated with the KPLPS (similar to82 and 95% of oral dose were absorbed for rats with KPLPS and control rats, respectively). (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.