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June 6, 2026Journal of Pharmaceutical SciencesOpen Access

A unified physiologically based pharmacokinetic model for low-to-high oral, subcutaneous, and intravenous dose of methotrexate in humans

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Authors

MKMin-Soo KimSWS.X. WangPMPaola Mian

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Overview

Randomized trial develops a pharmacokinetic model for methotrexate in humans, suggesting improved dose management.

Key Points

  • The study aims to create a comprehensive PBPK model for methotrexate that applies to a wide range of doses, improving understanding of its kinetics.
  • Developed a PBPK model using plasma and liver concentration data along with urinary excretion data from published sources.
  • Divided dataset into training and evaluation subsets for model assessment.
  • Calculated AAFE, AFE, and outlier percentages for model performance evaluation.
  • For the training dataset, AAFE was 1.55, AFE was 1.07, and percentage of outliers was 4.38%.
  • For the evaluation dataset, AAFE was 1.71, AFE was 1.17, and outliers were 9.68%.
  • The model is the first comprehensive MTX PBPK model that includes low to high doses, facilitating further applications.

Cite This Study

Kim et al. (2026) studied this question.

synapsesocial.com/papers/6a23b83e71a5da9775e7485bhttps://doi.org/10.1016/j.xphs.2026.104348
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