The metabolism of pivaloyloxymethyl (6
R, 7
R)-7-[(
Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(5-methy1-2
H-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
14C-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 urin.
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 fbces and metabolized mostly by β-lactamase produced from intestinal flora to unidentified metabelites. One of unidentified metabolites was assumed to be (
Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino-
N-formylmethylacetamide (T-2588G).
5-Methyl-1
H-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 (pivaloyhxymethyl-
14C)-T-2588 was orally given to rats and mice. It is assumed that HCHO, produced from
14CT-2588 by esterase, was metabolized to CO
2.
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