IN-VITRO METABOLIC N-OXIDATION AND C-OXIDATION OF PHENANTHRIDINE

The in vitro microsomal metabolism of phenanthridine has been studied to establish as to whether phenanthridine produces the corresponding N -oxide and lactam as metabolites and the mechanism involved, We now re port our preliminary findings using rat hepatic microsomal preparation s (control and induced with phenobarbitone) fortified with NADPH. The potential metabolite, phenanthridine-N-oxide, was prepared by m-CPBA o xidation of substrate; the lactam was commercially available. The subs trate and metabolites were extracted and analysed by HPLC and TLC. Fiv e metabolites, i.e. the corresponding N-oxide, lactam and three other products, were detected. Both N-oxide and lactam metabolites showed id entical chromatographic behaviour and UV spectrum - using a multi-arra y UV detector linked to a HPLC system - as the authentic compounds. Th e uncharacterised metabolites are proposed to be phenolic because of t heir chromatographic behaviour and response to detection reagents. The amount of N-oxide and lactam formed was significantly increased when phenobarbitone induced rat microsomes were used as enzyme source. The results indicate that these latter metabolites are probably formed by a phenobarbitone inducible CYP450 isozyme. It may be that the lactam w as produced via the N-oxide and experiments are under way to investiga te the proposed pathway.