title: Retrospective evaluation of methotrexate elimination when co-administered with proton pump inhibitors.
abstract: OBJECTIVE
  The aim was to assess potential interaction between methotrexate (MTX) and proton pump inhibitors (PPIs) in patients receiving high-dose MTX.
  
  
  METHODS
  Records of 56 adults receiving 201 cycles of MTX were reviewed to determine effects of PPI administration on MTX elimination. Repeated-measures logistic regressions and Cox regressions were performed to evaluate the possible drug interaction.
  
  
  RESULTS
  Despite a significant difference between those receiving a PPI and not receiving a PPI in median MTX levels at 24 (8.0 vs. 3.9 μmol l(-1) , respectively, P = 0.013) and 72 h after MTX administration (0.08 vs. 0.05 μmol l(-1) , respectively, P = 0.037), there was no difference between those receiving a PPI and not receiving a PPI in the proportion of patients experiencing delayed elimination at 24 (19.2% vs. 20.2%, respectively, P = 1.000) and 72 h (36.2% vs. 33.7%, respectively, P = 0.765). When data were analysed using Cox regression, controlling for multiple cycles of MTX per patient, PPI use was not a significant predictor of time to MTX < 0.1 μmol l(-1) . When the clustering effect of multiple cycles of MTX per patient was controlled for, co-administration of PPIs was not a significant predictor of MTX level (P = 0.969). A comparison of patients with delayed elimination at any time point and those without delayed elimination indicated that PPI use was not a significant predictor of delayed elimination (P = 0.607).
  
  
  CONCLUSIONS
  This study does not support previous findings of a significant interaction between PPIs and MTX. Based on these results, the clinical significance of any potential interaction is likely to be small.
authors.affiliation: College of Pharmacy and Health Sciences, Butler University, Indianapolis, IN, 46208, USA; St Vincent Indianapolis Hospital, Indianapolis, IN, 46260, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Reeves
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Moore
authors.forename: Devon
authors.initials: D
authors.lastname: Bascom
authors.forename: Brandon
authors.initials: B
authors.lastname: Rensing
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D054328:Proton Pump Inhibitors; D008727:Methotrexate
keywords: drug interaction; methotrexate; proton pump inhibitor