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.
Yu
D
D
Department of Pharmacology, Medical University of Lübeck, F.R.G.
Brasch
H
H
Iven
H
H
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D003484:Cyanamide / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006900:Hydroxylation; D007659:Ketones / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008727:Methotrexate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D007659:Ketones; D003484:Cyanamide; D000493:Allopurinol; C018637:phorone; D014969:Xanthine Oxidase; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase; D005978:Glutathione; D008727:Methotrexate