Studies on the metabolism of 883-S (ceruletide diethylamine) in rats.
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Metabolism of 883-S (ceruletide diethylamine) was studied in rats after intravenous administration of <SUP>14</SUP>C-883-S (alpha carbon of glycine residue was labeled with <SUP>14</SUP>C).<BR>The plasma level of unchanged 883-S rapidly decreased after injection. The level of unchanged 883-S was less than 10% of the total radioactivity present in the plasma 5min after injection. A major metabolite, present in plasma in the early phase, was a neutral peptide longer than tripeptide. One hour after injection, the radioactivity appeared in the plasma protein fraction, probably due to an extensive hydrolysis of 883-S and subsequent incorporation of <SUP>14</SUP>C-glycine moiety into the protein via biosynthetic pathway. In the urine, unchanged 883-S was not detected. The major urinary metabolite was ceruletide-(1-6) peptide, Pyr-Gln-Asp-Tyr (SO<SUB>3</SUB>H)-Thr-Gly. The radioactive metabolites in the bile were separated into two fractions. The major fraction contained unchanged 883-S, and the minor one contained ceruletide-(1-6) peptide, the same metabolite found in the urine.
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