title: Fever as a risk factor causing delayed elimination of methotrexate in pediatric patients receiving high doses of cancer chemotherapy.
abstract: OBJECTIVE
  Delayed elimination of methotrexate (MTX) has been reported to be caused by a number of factors. In order to identify these causes, we retrospectively investigated the risk factors for delayed elimination in pediatric patients who received high doses of MTX.
  
  
  METHODS
  The study included 69 courses of therapy involving 22 patients who received more than 1000 mg/m(2) of MTX. Plasma MTX concentrations 48 h (C48) and 72 h (C72) after infusion were used as indices of MTX elimination.
  
  
  RESULTS
  Neither C48 nor C72 was directly proportional to the dose of MTX infused. Both C48 and C72 were significantly higher in patients who developed fever of above 38 degrees C within a 10-day period (i.e., from 7 days before to 3 days after infusion) than in patients with no fever. Subgroup analysis revealed that C72 was significantly higher in patients who either developed fever and received antipyretics or developed fever but did not receive antipyretics than in patients who did not develop fever and did not receive antipyretics. Changes in the serum creatinine concentrations before and after MTX infusion revealed that renal function was significantly decreased in patients who developed fever compared to patients without fever.
  
  
  CONCLUSIONS
  The present results suggest that the development of fever is one of the main risk factors for the delayed elimination of MTX.
authors.affiliation: Department of Hospital Pharmacy, Mie University School of Medicine, 2-174 Edobashi Tsu-city, 514-8507 Mie, Japan. y-kagawa@clin.medic.mie-u.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Rika
authors.initials: R
authors.lastname: Mukohara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hori
authors.forename: Hajime
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
authors.forename: Michio
authors.initials: M
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000150:complications*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology / Q000502:physiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000188:drug therapy; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D003404:Creatinine; D008727:Methotrexate