Metabolism of oral cephalothin and related cephalosporins in the rat.

The fate of orally administered [(14)C]cephalothin has been studied in the rat. This antibiotic undergoes degradation in the gut followed by the subsequent absorption of a portion of the degradation products. About 50% of the administered radioactivity appears in the urine as a mixture of thienylacetylglycine, thienylacetamidoethanol and an unidentified polar metabolite. Evidence is presented indicating that thienylacetamidoethanol arises by the enzymic reduction of a metabolic intermediate, thienylacetamidoacetaldehyde. The metabolic fate of cephalothin is very similar to that of cephaloram reported earlier. The fate of [(14)C]cephaloridine and 7-phenoxy[1-(14)C]acetamidocephalosporin was also investigated. In addition to the expected metabolites, about 5% of the cephaloridine dose is absorbed unchanged. With 7-phenoxy[1-(14)C]acetamidocephalosporin, 15% of the dose is recovered in urine as deacetyl-7-phenoxy[1-(14)C]acetamidocephalosporin.