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Interference of high-dose methotrexate in the metabolism of valproate?

A case of tonic-clonic seizure was observed in a child with acute lymphoblastic leukemia a few hours after a 24-hour infusion of high-dose methotrexate (MTX; 5 g/m2). Because of former epileptic symptoms, the child had been treated with valproic acid for several months. During this and the following high-dose MTX infusion, an acute decline of the serum valproate concentration to about 25% of the pre-MTX value was observed. The pathogenesis of the acute decline of serum valproate concentration is discussed.