Abstract
Pharmacokinetic parameters of oltipraz were compared after intravenous and oral administration at a dose of 30mg/kg to control rats and rats with U-ARF. After intravenous administration to rats with U-ARF, the AUC was significantly greater (1100 versus 1730μg · min/mL) than that in control rats, and this could be due to significantly slower CL (27.2 versus 17.3mL/min/kg). The slower CL could be mainly due to significantly slower CLNR (27.2 versus 17.3mL/min/kg), and this could be supported by significantly slower in vitro CLint (32.1 versus 13.2mL/min/whole liver) in the rats. The Vss was significantly larger in rats with U-ARF (4050 versus 5680mL/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 149μg · 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).
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