ArticleCPT: pharmacometrics & systems pharmacology2025
Comprehensive Parent-Metabolite PBPK/PD Modeling Insights Into Methotrexate Personalized Dosing Strategies in Patients With Rheumatoid Arthritis.
Article in CPT: pharmacometrics & systems pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Low-dose methotrexate adverse reaction risk in renal impairment: pharmacovigilance and physiological pharmacokinetic model assessment.Frontiers in pharmacology · 2025Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid arthritis (RA) is a major public health concern, which can cause serious outcomes. Low-dose methotrexate (MTX) is a cornerstone in RA treatment, but there is significant heterogeneity in clinical response. To evaluate underlying sources of pharmacokinetic variability and clinical response of MTX, a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed using PK-sim and Mobi (version 11.1). The PBPK model included metabolism and transportation by AXO1, FPGS, GGH, RFC, and MRP2, with renal and biliary excretion. We also developed various degrees of renal insufficiency populations with subsequent dosing optimizations. A total of 23 MTX plasma concentration-time profiles were used, with 97% of predicted plasma concentrations within a two-fold range compared to observed data. The PBPK/PD modeling and simulation demonstrated that variability in renal clearance and enzymes related to MTX are likely important drivers of PK variability and there is a quantitative relationship between MTX-PG3 and RA treatment response. The PBPK/PD model could be used to guide improvement in MTX dose regimens for RA patients.
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Registered trials
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