The pharmacokinetics of i.v. and p.o. methotrexate (MTX) in humans is reported. The plasma concentration profile following the two routes of administration was parallel with a mean final half-life of 24.9 hr. Absorption of tritiated MTX from solution is complete at a dose of 30 mg MTX per sq m body surface area. At the higher dose of 80 mg/sq m only 31% of the dose was absorbed in the one patient studied. The amount of metabolites formed after i.v. administration is negligible at 6% of the dose. In contrast, following p.o. administration, 35% of the absorbed dose is excreted as metabolites. Metabolism of p.o. MTX in the gastrointestinal tract or during the first pass through the liver is suggested as possible events.

The presence of malignant effusions could contribute to inter-individual variation in pharmacokinetics.

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Supported in part by Contract NCI-C-71-2184 and Grants GM 15956 and CA 12644 from the USPHS.

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