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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 Vss 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.