Effects of acute renal failure on the pharmacokinetics of oltipraz in rats.
Pharmacokinetic parameters of oltipraz were compared after intravenous and oral administration at a dose of 30 mg/kg to control rats and rats with U-ARF. After intravenous administration to rats with U-ARF, the AUC was significantly greater (1100 versus 1730 microg x min/mL) than that in control rats, and this could be due to significantly slower CL (27.2 versus 17.3 mL/min/kg). The slower CL could be mainly due to significantly slower CL(NR) (27.2 versus 17.3 mL/min/kg), and this could be supported by significantly slower in vitro CL(int) (32.1 versus 13.2 mL/min/whole liver) in the rats. The Vss was significantly larger in rats with U-ARF (4050 versus 5680 mL/kg), and this was not due to a significant increase in free fractions (unbound in plasma proteins) of oltipraz in the rats because the free fractions were 17.0 and 15.7% for control rats and rats with U-ARF, respectively. Unexpectedly, after oral administration to rats with U-ARF, the AUC of oltipraz was significantly smaller than that in control rats (329 versus 149 microg x min/mL), and this could be mainly due to a decrease in the absorption of oltipraz from the gastrointestinal tract in the rats (95 and 72% of the oral dose were absorbed in control rats and rats with U-ARF, respectively).
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Ding, Kwanak-Gu, Seoul 151-742, South Korea.
Soo K
SK
Bae
Shin J
SJ
Lee
Jin W
JW
Kim
Young H
YH
Kim
Sang G
SG
Kim
Myung G
MG
Lee
D058186:Acute Kidney Injury / Q000097:blood*; D000818:Animals; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013871:Thiones; D013876:Thiophenes
D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz