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 microg min/ml versus 7440 microg min/ml), and this was not due mainly to a decrease in absorption from the gastrointestinal tract in rats with U-ARF.
Bae
Soo K
SK
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Kwon
Jong W
JW
Kim
Won B
WB
Lee
Inchul
I
Lee
Myung G
MG
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014502:Uranyl Nitrate
D000890:Anti-Infective Agents; C480487:DA-7867; D023303:Oxazolidinones; D014502:Uranyl Nitrate