Pharmacokinetic Studies of [14C]Urea. (1); Absorption, Distribution, Metabolism and Excretion after Single Administration of [14C]Urea in Fasted Rats.

Abstract

Absorption, distribution, metabolism and excretion after a single intravenous and oral administration of [14C]urea at a main dose of 2 mg/kg were investigated in non-fasted rats. Comparison of the pharmacokinetics in rats between under non-fasted and fasted conditions was also investigated. 1. The radioactivity levels in plasma were decreased biphasically with t1/2α of 2-3 hr and t1/2β of 6-11 hr, irrespective of administration routes and doses. After oral administration at doses of 2, 62.5, 250 and 1000 mg /kg, the Cmax and AUC0-∞ were virtually proportional to the administered doses, suggesting linear-pharmacokinetics within the examined dose range. 2. The radioactivity levels in plasma and tissues reached Cmax at 0.5-1 hr after oral administration. The concentration in the kidney, which was 2.4 times as high as that in plasma, was the highest in the examined tissues. The concentrations in other tissues were similar to, or lower than the plasma concentration. After the Cmax, the concentrations in most tissues decreased in almost parallel with the plasma concentration. 3. In plasma at 1 hr after oral administration, only the unchanged drug was observed in the plasma radioactivity. On the other hand, at 8 hr, about 70% and 30% of the plasma radioactivity were unchanged drug and unknown components, respectively. In urine for 24 hr after dosing, only the unchanged drug was also observed, irrespective of administration routes. 4. Within 96 hr, 73.1%, 1.6% and 20.1% of dosed radioactivity were excreted in urine, feces and expired air after intravenous administration, and 54.0%, 1.0% and 42.9% after oral administration, respectively. The bioavailability estimated from the ratio of urinary excretion of urea after oral administration to that after intravenous administration was 74%. 5. Feeding condition in rats enhanced metabolism/decomposition of urea and influenced its plasma concentration-time profiles and excretion profile.