Enzymatic reduction of chloramphenicol and nitrosochloramphenicol by rat liver microsomal preparations.
Chloramphenicol (CAP) and nitrosochloramphenicol (NO-CAP) were metabolically reduced to aromatic amines by rat liver microsomes in vitro. The reduction required anaerobic conditions and was mediated by a NADPH-dependent reductase system. Both CAP and NO-CAP reduction were time and concentration dependent. Compared to CAP, NO-CAP (0.5 mM) reduction was rapid with complete conversion occurring in 90-120 min. At 2.5 mM NO-CAP reduction was depressed. In the presence of NO-CAP (0.05-2.5 mM) CAP metabolism was inhibited from 17 to 91%. These results indicate that CAP and NO-CAP are metabolized by similar microsomal reductase systems and NO-CAP is unstable, readily reduced further to the aromatic amine.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002701:Chloramphenicol / Q000031:analogs & derivatives* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D002701:Chloramphenicol; C026099:nitrosochloramphenicol