Disposition of urea following intravenous administration to rats

To evaluate the distribution, metabolism and excretion of urea in normal rats, plasma concentration profiles, whole-body autoradiograms and urinary, fecal and expiratory excretions following intravenous administration of 14C-urea were investigated. High (1000 mg/kg) and low (0.0675 or 0.117 mg/kg) doses of urea were employed to examine dose-induced differences in the plasma levels and in the whole-body autoradiograms. Plasma radioactivity-time curves were analyzed according to a two-compartment open model. There were no significant differences in almost all of the pharmacokinetic parameters for these two doses. Even in the case of parameters with significant differences (α, β and k10), the dose dependency was considered to be rather small. When these parameters are compared with those for creatinine, k12 and k21 (which are both transfer rate constants for urea between plasma and tissue compartments) were significantly larger than those for creatinine, while (Vd')extrap for urea was about one-third of that for creatinine. There was also no significant dose dependency in the whole-body autoradiograms. The distribution pattern of urea radioactivity was almost uniform except in the kidney and urinary bladder even at an early stage (at 5 and 20 min). Following the intravenous doses, urea was regarded as being eliminated predominantly via the renal route, since more than 80% of the dose was excreted into the urine in 24 h. However, expiratory excretion of the radioactivity was about 12% in 24 h following i.v. administration of 14C-urea, while that after p.o. administration was approximately 37%.