Abstract
Absorption, distribution and excretion of omeprazole, a potent antiulcer agent, were investigated in rats after oral administration of 14C labeled compound (14C-OPZ).
Urinary and fecal recoveries of radioactivity (14C) within 4 days at a dose of 5 mg/kg were about 22% and 72% after po dose, about 32 % and 66 % after iv dose, respectively. In male rats, urinary excretion had a tendency to increase under the fasting condition and the higher dose levels.
About 48 % of dose was excreted in the bile of male rats during 30 hours after oral dose of 5 mg/kg, and about 26 % of 14C excreted in the bile was reabsorbed from the intestines due to enterohepatic circulation.
Peak plasma levels of 14C was reached within 0.5 hour, and the radioactivity was eliminated with the terminal half-lives (T1/2) of 23.1 ?? 30.9 hours after oral dose. A significant increase in Cmax and AUC's was found, exceeding the expected values proportional to administered dose.
High levels of 14C were observed in the liver, kidney, urinary bladder and gastrointestinal tracts, but there was no evidence of an accumulation of 14C in any tissues after oral administration. Tissue distribution pattern of 14C in female rats was similar to that in male rats. The level of 14C in the milk of lactating rats was slightly higher than that in the plasma. The level of 14C in the placenta and tissues in fetuses was lower than that in the maternal blood or plasma.
No significant quantitative and qualitative differences in urinary metabolite pattern were observed among dose levels, but a slightly quantitative difference was observed between males and females.
