No influence of enzyme inhibitors on the hydroxylation of methotrexate in rats.

In anaesthetized rats 50% of an infused dose of methotrexate (MTX) was excreted into the bile. About 3% was metabolized to 7-hydroxymethotrexate (7-OH-MTX), which appeared also in the bile. Pretreatment with allopurinol had no influence on the elimination of MTX or the production of 7-OH-MTX during a 3-h infusion of MTX. Cyanamide decreased the total MTX clearance, but increased the biliary elimination of 7-OH-MTX. Phorone decreased the biliary MTX-clearance, but not the biliary secretion of 7-OH-MTX. The results show that neither aldehyde oxidase nor xanthine oxidase is the predominant hydroxylating enzyme for MTX in the rat.