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August 9, 2026Modern RheumatologyOpen Access

Population pharmacokinetic analysis of factors affecting the clearance of methotrexate polyglutamates in red blood cells in Japanese patients with rheumatoid arthritis

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Authors

JHJun HakamataJikei University School of MedicineYKYuko KanekoKeio UniversityMSMikiko ShimizuFujita Health University

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Overview

Population pharmacokinetic study reveals determinants of methotrexate polyglutamate clearance in rheumatoid arthritis, suggesting clinical factors guide personalized dosing.

Key Points

  • To identify clinical and genetic factors influencing the apparent clearance of total methotrexate polyglutamates in red blood cells among Japanese patients with rheumatoid arthritis.
  • Enrolled 268 Japanese patients with rheumatoid arthritis undergoing low-dose methotrexate therapy.
  • Measured red blood cell concentrations of methotrexate polyglutamates using liquid chromatography–tandem mass spectrometry and modeled kinetics with Phoenix NLME software.
  • Evaluated patient covariates and genetic polymorphisms in drug transporters (RFC1, ABCB1, ABCC2, ABCG2) and metabolic enzymes (FPGS, GGH).
  • Identified body weight, estimated glomerular filtration rate, and proton pump inhibitor co-administration as significant covariates for apparent clearance.
  • Observed that lower body weight, reduced glomerular filtration rate, and concurrent proton pump inhibitor therapy significantly decreased clearance.
  • Found that evaluated genetic polymorphisms in drug transporters and enzymes were not significant covariates for clearance.

Cite This Study

Hakamata et al. (2026) studied this question.

synapsesocial.com/papers/6aaa054fb5e32d7ae6558964https://doi.org/10.1093/mr/roag063
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