Effects of acute renal failure on the pharmacokinetics of oltipraz in rats

✍ Scribed by Soo K. Bae; Shin J. Lee; Jin W. Kim; Young H. Kim; Sang G. Kim; Myung G. Lee

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 147 KB
• Volume: 93
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20141

✦ Synopsis

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 mg Á 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 V ss 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 mg Á 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).