The metabolism of pivaloyloxymethyl (6R, 7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(5-methyl-2H-tetrazol-2-yl)methyl]-3-cephem-4-carboxylate (T-2588), a new oral esterified cephalosporin of T-2525 as a prodrug, was studied with 14C-T-2588. 14C-Activity was recovered mostly in the feces, a little in the urine and slightly in the bile, when (aminothiazole-2-14C)-T-2588 was orally given to rats and mice. 14C-T-2588 was rearranged to 14C-T-2588A by gastrointestinal content. 14C-T-2588 and 145C-T-2588A were absorbed at the upper intestine, and hydrolyzed to 14C-T-2525 and 14C-T-2525A, respectively, by esterase in the intestinal mucosa. 14C-T-2525 and 14C-T-2525A were circulated in whole body and excreted into the urine. On the other hand, unabsorbed 14C-T-2588 and 14C-T-2588A were hydrolyzed by esterase in the intestinal tract to 14C-T-2525 and 14C-T-2525A, respectively, which were excreted partly in the feces and metabolized mostly by .beta.-lactamase produced from intestinal flora to unidentified metabolites. One of unidentified metabolites was assumed to be (Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino-N-formylmethylacetamide (T-2588G). 5-Methyl-1H-tetrazole (T-2588F) and pivalic acid were produced together with liberation of T-2588G, and absorbed at the intestine. Unchanged T-2588F and conjugated pivalic acid were excreted into the urine. 14C-Activity was almost recovered in respiratory air, when (pivaloyloxymethyl-14C)-T-2588 was orally given to rats and mice. It is assumed that HCHO, produced from 14C-T-2588 by esterase, was metabolized to CO2.
