Effects of acute renal failure on the pharmacokinetics of DA‐7867, a new oxazolidinone, in rats

The pharmacokinetic parameters of DA‐7867 were compared after intravenous and oral administration at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (rats with U‐ARF). After intravenous administration in rats with U‐ARF, the time‐averaged total body clearance ( Cl ) was significantly faster (2.45 versus 0.932 ml/min/kg) than controls due to significantly faster nonrenal clearance (2.25 versus 0.855 ml/min/kg) in rats with U‐ARF. The faster nonrenal clearance could be due to significantly greater gastrointestinal (including biliary) excretion; the amount of unchanged DA‐7867 recovered from the entire gastrointestinal tract at 24 h was significantly greater (30.3% versus 9.38% of intravenous dose) in rats with U‐ARF. In rats with U‐ARF, the V ss was significantly larger (1420 ml/kg compared with 580 ml/kg), but this was not due to a difference in plasma protein binding; the values were comparable between the two groups of rats. After oral administration to rats with U‐ARF, the total area under the plasma concentration‐time from time zero to time infinity ( AUC ) of DA‐7867 was significantly smaller than the controls (2560 µg min/ml versus 7440 µg min/ml), and this was not due mainly to a decrease in absorption from the gastrointestinal tract in rats with U‐ARF. Copyright © 2005 John Wiley & Sons, Ltd.