title: Pharmacokinetics of erythrocyte methotrexate in children with acute lymphoblastic leukemia during maintenance treatment.
abstract: The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured in 47 children with acute lymphoblastic leukemia during maintenance treatment with MTX 1.7-21.6 mg/m2/week and 6-mercaptopurine 25-75 mg/m2/day. At the time of measurement the plasma MTX concentration was less than 2 nmol/l. The steady state E-MTX varied between 51 and 202 nmol/l erythrocytes. Alterations in the E-MTX took place over 8-12 weeks after a change in dosage. A significant correlation was found between the E-MTX and the weekly dose of MTX administered. Noncompliance was revealed in two patients. A very low E-MTX was found in one patients, probably caused by inhibition of erythropoiesis. No correlation was found between E-MTX and the total amount of MTX administered or the length of treatment. A terminal half-life of 2-5 weeks after discontinuation of the drug showed that the erythrocytes functioned as a slow-changing compartment for MTX. Unexpectedly low E-MTX could mean noncompliance, impaired erythropoiesis, altered metabolism, or poor drug absorption.
authors.forename: H
authors.initials: H
authors.lastname: Schrøder
authors.forename: N
authors.initials: N
authors.lastname: Clausen
authors.forename: E
authors.initials: E
authors.lastname: Ostergaard
authors.forename: T
authors.initials: T
authors.lastname: Pressler
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D008727:Methotrexate