In addition to cytochrome P450, oxidation of drugs and other xenobioti
cs can also be mediated by non-450 enzymes, the most significant of wh
ich are flavin monooxygenase, monoamine oxidase, alcohol dehydrogenase
, aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase. This
article highlights the importance of these non-P450 enzymes in drug me
tabolism. A brief introduction to each of the non-P450 oxidizing enzym
es is given in this review and the oxidative reactions have been illus
trated with clinical examples. Drug oxidation catalyzed by enzymes suc
h as flavin monooxygenase and monoamine oxidase may often produced the
same metabolites as those generated by P450 and thus drug interaction
s may be difficult to predict without a clear knowledge of the underly
ing enzymology, in contrast, oxidation via aldehyde oxidase and xanthi
ne oxidase gives different metabolites to those resulting from P450 hy
droxylation. Although oxidation catalyzed by non-P450 enzymes can lead
to drug inactivation, oxidation may be essential for the generation o
f active metabolite(s). The activation of a number of prodrugs by non-
P450 enzymes is thus described. It is concluded that there is still mu
ch to learn about factors affecting the non-P450 enzymes in the clinic
al situation.