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Retrospective evaluation of methotrexate elimination when co‐administered with proton pump inhibitors
Author(s) -
Reeves David J.,
Moore Elizabeth S.,
Bascom Devon,
Rensing Brandon
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12384
Subject(s) - medicine , methotrexate , logistic regression , gastroenterology , proton pump inhibitor , antifolate , retrospective cohort study , pharmacokinetics , pharmacology , antimetabolite
Aims The aim was to assess potential interaction between methotrexate ( MTX ) and proton pump inhibitors ( PPI s) 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 C ox 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.