Reductive dechlorination of chloramphenicol by rat liver microsomes

Drug Metab Dispos. 1983 Mar-Apr;11(2):126-30.

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.

MeSH terms

  • Aerobiosis
  • Anaerobiosis
  • Animals
  • Biotransformation
  • Chloramphenicol / metabolism*
  • Chlorine / metabolism
  • Chromatography, High Pressure Liquid
  • In Vitro Techniques
  • Male
  • Mass Spectrometry
  • Microsomes, Liver / metabolism*
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains

Substances

  • Chlorine
  • Chloramphenicol