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

摘要

Absorption, distribution, metabolism and excretion after a single intravenous and oral administration of [~14C] urea at a dose of 2 mg/kg were investigated in fasted rats.1.Both radioactivity levels in plasma after intravenous and oral administration of [~14C] urea were decreased biphasically with t_(1/2#alpha#) of about 2.0 hr had t~(1/2#beta#) of about 3.5 hr. After oral administration, the plasma concentration reached C_max at 0.5 hr, suggesting rapid absorption of urea in the gastrointestinal tract.2.Radioactivity levels in most tissues reached C_max at 0.5 hr after oral administration, similar to that observed in the plasma. Excluding the radioactivity present in the digestive tract where [~14C] urea was administered, the concentrations in the kidney and urinary bladder were the highest in the examined tissues and were 3.2 and 2.5 times as high as that in plasma. The concentrations in other tissues were similar to , or lower than the plasma concentration. Subsequently, the concentrations in most tissues rapidly decreased in parallel with the plasma concentration.3.In plasma at 0.5 hr and 8hr after oral administration and in the urine collected for 24 hr after intravenous and oral administration, the major component of radioactivity was the unchanged drug and other metabolites were not observed. One may concluded that urea was almost not metabolized in fasted rats, considering the results of the excretion study, in which more than about 90% of dose radioactivity was excreted in urine as unchanged drug.4.Within 96 hr, 91.1%, 0.3% and 4.7% of dosed radioactivity were excreted in urine, feces and expired air after intravenous administration, and 95.1%, 1.2% and 3.5% after oral administration, respectively. The bioavailability estimated from the ratio of urinary excretion of urea after oral administration to that after intravenous administration was almost 100%.