Article date: March 1992
By: P Honkakoski, P Arvela, R Juvonen, MA Lang, M Kairaluoma, O Pelkonen, in Volume 33, Issue 3, pages 313-317
1. The contribution of human P450 2A6 and mouse P450 2a‐5 isoenzymes, both highly active in coumarin 7‐hydroxylation, to the metabolism of warfarin was studied in several in vitro systems with human and mouse liver preparations. 2. The reconstituted P450 2a‐5 purified from DBA/2 mouse liver did not metabolize warfarin. 3. An anti‐P450 2a‐5 antibody did not consistently inhibit any of the warfarin biotransformation reactions catalyzed by human or mouse liver microsomes, although coumarin 7‐hydroxylation was inhibited by over 90%. 4. In some human microsomal samples, 4‐ and 8‐hydroxylations of warfarin were inhibited to some extent by the anti‐P450 2a‐5 antibody. 5. Warfarin (less than 1 mM) did not inhibit coumarin 7‐hydroxylation by human or mouse liver microsomes in vitro. 6. We conclude that mouse and human coumarin 7‐ hydroxylases do not oxidise warfarin.
DOI: 10.1111/j.1365-2125.1992.tb04042.x
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