title: The transport and accumulation of methotrexate in human erythrocytes.
abstract: The uptake of methotrexate (MTX) by human erythrocytes was studied in vivo and in vitro. Following a pulse intravenous injection of MTX in two subjects, MTX accumulated rapidly in erythrocytes and its intracellular concentration declined at a slower rate than the serum concentration. Twenty-four hours later erythrocytes had no MTX but the drug reappeared 3-7 days later. In subjects receiving twice monthly MTX, the drug accumulated in the erythrocytes as protein-bound (61%) and nonprotein bound (39%) forms. The latter is presumably MTX-polyglutamate. In vitro, MTX uptake by erythrocytes was virtually absent at plasma concentrations of 1 nM-1 micro M, but uptake increased substantially above 10 micro M by a mechanism which was not saturated even at 1 mM. The major fraction of MTX which accumulated by erythrocytes in vitro effluxed during the first minute and was not protein-bound, unlike MTX which accumulated in vivo. This suggests that MTX binds to a protein in developing erythroblasts which contain dihydrofolate reductase and that the delayed appearance of MTX in circulating erythrocytes following in vivo administration corresponds to bone marrow maturation time of erythroblasts.
mesh_terms: D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D005492:Folic Acid / Q000097:blood; D006801:Humans; D008727:Methotrexate / Q000097:blood*; D013997:Time Factors
chemical_list: D005492:Folic Acid; D008727:Methotrexate