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To the Editor.—
We recently became aware of the paper by Halprin KW et al, (Arch Derm 103:243-249, 1971), wherein the pharmacokinetics of methotrexate are described. They observed a rather short half-life (two to ten hours) for methotrexate following both oral and intramuscular administration.Based upon recent studies in our laboratory with use of tritium-labeled methotrexate, we wish to report that the plasma half-life for methotrexate in man is considerably longer than that reported. In 18 patients, the plasma disappearance of methotrexate is biphasic with the short half-life (representing drug distribution) of about one-half hour and the long plasma half-life (representing drug elimination) of 25 to 30 hours. The half-life value reported by Halprin et al most likely represents the distributive phase rather than the longer and more important half-life. In addition, we have examined the fluorometric method and find that its lower limit of sensitivity is 0.1μg/ml. Since it