The pharmacology of 3H-labeled methotrexate (MTX-3H) has been studied in 10 patients with inoperable solid tumors. Absorption of the drug at the 0.1 mg/kg doses routinely employed in clinical practice is comparable following either p.o. or i.v. administration. At larger doses gastrointestinal absorption is incomplete. Plasma levels following i.v. or small p.o. doses are directly dose-related with a mean plasma half-time of 134 min for MTX. From 54 to 88% of an i.v. or small p.o. dose is excreted in the urine during the 1st 24 hr. A smaller amount (4–24%) appears in subsequent urines and in the stool.

MTX is 50% bound to serum proteins over a range of concentrations encompassing those seen clinically. MTX distributes itself to total body water within 1 hr following an i.v. or small p.o. dose.

Three urinary metabolites, totaling 10% of the total radioactivity in the sample, were seen in 1 of 9 chromatographic studies. Reasons are presented for considering these to be the result of in vitro bacterial or chemical conversion, rather than the result of in vivo metabolism.

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Presented in part at the 64th Annual Meeting, American Association for Cancer Research, Toronto, Canada, May, 1963.

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