Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure

Abstract

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg) administration to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on the basis of physiological parameters. After intravenous administration of YJA-20379-8, the pharmacokinetic parameters were not significantly different between two groups of rats except significant increase in volume of distribution at steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126 versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8 from gastrointestinal tract; the percentages of oral dose of YJA-20379-8 recovered from gastrointestinal tract at 24 hr as unchanged drug was significantly greater (19.9% versus 6.61%) in rats with U-ARF.