Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans

This study deals with individual and species variations in the converting a ctivity of methotrexate (MTX) to 7-hydroxymethotrexate in animals acid huma ns. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 38-fo ld range of intersubject variation of the activity was observed. The variat ions were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate, Species difference s of Liver MTX 7-hydroxylase activity were also observed, The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetec table in dogs. Strain differences of MTX 7-hydroxylase activity based on al dehyde oxidase activity were also observed in rats and mice. The results su ggest that aldehyde oxidase functions as MTX: 7-hydroxylase in livers of an imals and humans, and the observed differences of MTX 7-hydroxylase activit y are due to variations in the amount of aldehyde oxidase present.