Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans |
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Authors: | Kitamura S Sugihara K Nakatani K Ohta S Ohhara T Ninomiya S Green C E Tyson C A |
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Affiliation: | Institute of Pharmaceutical Science, Hiroshima University School of Medicine, Japan. kitamura@pharm.hiroshima-u.ac.jp |
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Abstract: | This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7-hydroxymethotrexate in animals and humans. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 48-fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate. Species differences of liver MTX 7-hydroxylase activity were also observed. The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7-hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX 7-hydroxylase in livers of animals and humans, and the observed differences of MTX 7-hydroxylase activity are due to variations in the amount of aldehyde oxidase present. |
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