Urinary Metabolites of 1-(3-Mercapto-2-D-methyl-1-oxopropyl)-L-proline (SQ-14225), a New Antihypertensive Agent, in Rats and Dogs

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The in vivo metabolism of 1-(3-mercapto-2-D-methyl-1-oxopropyl)-L-proline (SQ-14225) was investigated in rats and dogs. SQ-14225 labeled with ^<14>C at the mercaptoacyl moiety was administered orally and the metabolites in the 24 hr urine were identified by comparing their Rf values with those of authentic samples. Unchanged SQ-14225 was trapped via its sulfhydryl group by the previous addition of N-ethylmaleimide to prevent air oxidation. In both animal species, most of the radioactivity was excreted as unchanged SQ-14225 and its disulfide (SQ-14551). A significant amount of the urinary radioactivity was accounted for by mixed disulfides, among which the disulfide with L-cysteine (Cys-SQ-14225) was predominant. N-Acetyl-Cys-SQ-14225 was also detected as a minor component, but the amount of the mixed disulfide with glutathione (GS-SQ-14225) was negligible. S-Methyl-SQ-14225 and its sulfoxide were also recognized. As judged from the negligible incorporation of radioactivity into collagen after administration of SQ-14225-^3H labeled at the proline moiety, the metabolic cleavage of the amide bond in SQ-14225 was not significant.
社団法人日本薬学会の論文
1981-05-23