Disposition of Urea following Intravenous Administration to Rats

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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 ^<14>C-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 k_<10>), the dose dependency was considered to be rather small. When these parameters are compared with those for creatinine, k_<12> and k_<21> (which are both transfer rate constants for urea between plasma and tissue compartments) were significantly larger than those for creatinine, while (V_d')_<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 ^<14>C-urea, while that after p.o. administration was approximately 37%.
社団法人日本薬学会の論文
1982-04-25

Disposition of Urea following Intravenous Administration to Rats

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