Pharmacokinetics of oltipraz after intravenous and oral administration in rats with dehydration for 72 hours

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Abstract
Pharmacokinetic parameters of oltipraz were compared after intravenous and oral administration at a dose of 30 mg/kg to control rats and rats with water deprivation for 72 h (rats with dehydration). The plasma protein binding of oltipraz was measured in both groups of rats using an equilibrium dialysis technique. The concentrations of oltipraz were measured by the reported HPLC analysis. After intravenous administration, the total area under the plasma concentration–time curve from time zero to time infinity (AUC), terminal half‐life, time‐averaged total body and nonrenal clearances, and apparent volume of distribution at steady state were not significantly different between the two groups of rats. However, after oral administration to rats with dehydration, the AUC was significantly smaller than that in control rats (180 versus 316 µg min/ml) mainly due to decrease in absorption. In rats with dehydration, plasma protein binding was significantly greater than that in control rats (91.5 ± 0.309 versus 81.3 ± 2.79%). Copyright © 2004 John Wiley & Sons, Ltd.