Aldehyde Oxidase‐catalysed Oxidation of Methotrexate in the Liver of Guinea‐pig, Rabbit and Man

Although 7‐hydroxymethotrexate is a major metabolite of methotrexate during high‐dose therapy, negligible methotrexate‐oxidizing activity has been found in‐vitro in the liver in man. The goals of this study were to determine the role of aldehyde oxidase in the metabolism of methotrexate to 7‐hydroxymethotrexate in the liver and to study the effects of inhibitors and other substrates on the metabolism of methotrexate. Methotrexate, (±)‐methotrexate and (‐)‐methotrexate were incubated with partially purified aldehyde oxidase from the liver of rabbit, guinea‐pig and man and the products analysed by HPLC. Rabbit liver aldehyde oxidase was used for purposes of comparison.

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