Metabolic conversion of methotrexate in man.

Metabolism of methotrexate (MTX) to closely related analogues has been increasingly recognized in recent years. 7-Hydroxymethotrexate, 2,4-diamino-N10-methylpteroic acid, and methotrexate poly-gamma-glutamates have been established as products of metabolic conversion in man. The significance of the formation of these metabolites has not been firmly established. Certain of these compounds may play a role in the development of the renal failure syndrome associated with high-dose infusions, contribute to the chronic toxicity of MTX administration, and cross-react to a significant degree in radioimmunoassay methods for measurement of MTX concentrations.