DISTRIBUTION OF CREATININE FOLLOWING INTRAVENOUS AND ORAL ADMINISTRATION TO RATS

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To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-^<14>C] creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 μg/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k_<12> and k_<21>, which are transfer rate constants between compartment 1 and 2,for creatinine were significantly smaller than those of urea. On the other hand, k_<10> was larger in creatinine. Furthermore, (V'_d)_<extrap> for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k_<12> and k_<21> than creatinine.
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DISTRIBUTION OF CREATININE FOLLOWING INTRAVENOUS AND ORAL ADMINISTRATION TO RATS

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