title: Potential interaction between methotrexate and omeprazole.
abstract: OBJECTIVE
  To report a case of delayed elimination of high-dose methotrexate (MTX) associated with concomitant omeprazole administration.
  
  
  METHODS
  Delayed MTX elimination was observed in an 11-year-old white boy who concomitantly received high-dose MTX and omeprazole. The patient's serum creatinine and liver function tests were normal during treatment and follow-up. The only medication we suspected of inhibiting MTX elimination was omeprazole 20 mg every 12 hours. Twenty-four hours after the first high-dose MTX cycle (15 g), omeprazole was discontinued. Thereafter, the patient received one high-dose MTX cycle without omeprazole every month for five months; MTX elimination was normal throughout MTX cycles 2 to 5.
  
  
  CONCLUSIONS
  MTX is actively secreted in the distal tubules. The renal hydrogen/potassium adenosine triphosphatase (H+/K(+)-ATPase) pump makes the urine more acidic, by secreting hydrogen ions into the renal tubule and reabsorbing potassium ions. Active tubular secretion of MTX requires the activity of this pump because MTX is excreted with hydrogen ions. Omeprazole can inhibit renal elimination of the hydrogen ion and block the active tubular secretion of MTX. Therefore, the elimination half-life of MTX increases, which may result in potentially toxic concentrations of MTX. At a pH of approximately 5, as found in the renal tubules, pantoprazole is more slowly activated than omeprazole, reducing the incidence of unwanted reactions with sulfhydryl groups and adverse effects occurring outside of the gastric hydrogen pump.
  
  
  CONCLUSIONS
  Based on the Naranjo probability scale, a probable drug interaction was observed. Omeprazole may delay MTX elimination; therefore, when prescribing MTX, an alternative to omeprazole should be considered.
authors.affiliation: Pharmacy Department, University Hospital of Navarra, Pamplona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Beorlegui
authors.forename: A
authors.initials: A
authors.lastname: Aldaz
authors.forename: A
authors.initials: A
authors.lastname: Ortega
authors.forename: I
authors.initials: I
authors.lastname: Aquerreta
authors.forename: L
authors.initials: L
authors.lastname: Sierrasesúmega
authors.forename: J
authors.initials: J
authors.lastname: Giráldez
mesh_terms: D002648:Child; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009853:Omeprazole / Q000494:pharmacology* / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy
chemical_list: D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D009853:Omeprazole; D008727:Methotrexate