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Please correct me if I am wrong. I thought that the main player for
nitroreduction is
not oxidative cytochrome P450 isoenzymes, but nitro-reductase(s).
It is believed that nitro-reduction is carried out mainly by reductases
in the
liver and gut:
a) Liver: by microsomal nitro reductases system which appears to consist of
at least 3 components:
- NADPH-cytochrome C reductase, Cyt P-450 (anaerobic conditions), poorly
characterised NADPH-dependent microsomal nitro reductases,
and by \0x01+soluble\0x01, nitro reductases such as xanthine oxidase and
aldehyde
oxidase.
b) Intestine: NADPH-dependent bacterial reductase
Aromatic nitro group reduction requires a 6 electrons transfer to obtain
the
terminal amino compound (CYP enzymes could be the potential electron
recipients). The
various intermediates in the reduction include nitroso and hydroxylamine.
What critical role does the most prevalent CYP isoenzymes such as 2D6
or 3A3/4 play in nitro-reduction? If a compound primarily undergoes
nitro-reduction,
will the coadministration of a CYP2D6 or 3A3/4 inhibitor inhibits the
nitro-reduction
of the compound clinically?
Will appreciate the response.
Charles Oo, PharmD, PhD,
Hoffmann La-Roche Inc.
340, Kingsland Street
Nutley, NJ 07110-1199
Tel: 201-5622575
Fax: 201-562-2325
Email: Charles.oo.-at-.roche.com
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