| Abstract: | When chloramphenicol was incubated with rat liver microsomes anaerobically, it was metabolized predominantly to deschloro-chloramphenicol and products that become irreversibly bound to microsomal protein. Cytochromes P-450 induced by phenobarbital appeared to catalyze these reactions most effectively. Glutathione increased the formation of deschloro-chloramphenicol by 13% and decreased the amount of the irreversibly bound product by 18%, respectively. Only a small amount of the nitroaromatic-reduced product, chloramphenicol amine, was detected by high pressure liquid chromatography. These results are consistent with chloramphenicol being biotransformed and activated by cytochromes P-450 anaerobically through predominantly reductive dechlorination. |
