SOME OBSERVATIONS ON HUMAN PHARMACOLOGY OF METHOTREXATE

Abstract

Plasma and urinary levels of methotrexate (MTX) were measured enzymatically in 18 cancer patients receiving doses of 5-1250 mg. When 3H-labeled MTX was administered, plasma levels measured by radioisotope counting were significantly higher than those measured enzymatically, the difference being accounted for by the presence of 3H label in plasma water as a result of drug metabolism. Renal clearance of MTX correlated well with glomerular filtration rate (GFR) and was consistently lower than the GFR, suggesing tubular reabsorption of the drug at the rate of urine flow studied. Plasma clearance measured by an infusion method was consistently greater than renal clearance, suggesting drug metabolism. Biliary MTX levels were measured in 3 patients and were much higher than plasma levels, suggesting a quantitatively important biliary recirculation of the drug. Plasma levels of MTX measured after 24 h were not significantly different following i.v. or i.m. administration, but were higher if an infusion was used.