Comparative metabolism of chloramphenicol in germfree and conventional rats

The action of gut microflora on the metabolism of chloramphenicol (CP) was studied in germfree (GF) and conventional (CV) rats after administration of single oral doses of tritiated CP. There were similarities in the metabolic pathways of CP in the GF and CV animals, i.e., rapid absorption, hepatic glucuroconjugation, and biliary excretion of the CP conjugate. CP, CP-oxamic acid, CP-alcohol, and CP-base were present in similar proportions in the urine of both GF and CV rats. Differences observed included the slow elimination of total radioactivity and a reduced proportion of the urinary excretion versus the fecal excretion in the GF Reduction products which were present in much greater quantities in the urine and feces of CV rats are compatible with the generally described hydrolysis of the CP-glucuronide, followed by a nitroreduction of the CP by the gut microflora and the reabsorption of a part of the products formed. In GF rats, CP-glucuronide was the major fecal metabolite, a portion of it having been reabsorbed and excreted in the urine. Although in lesser amounts, reduction products were still present as urinary metabolites in GF rats. Such a reduction in the tissues might produce active intermediate that could be related to CP toxicity.