ArticleBiopharmaceutics & drug disposition2013
Pharmacokinetics, pharmacodynamics and toxicities of methotrexate in healthy and collagen-induced arthritic rats.
Article in Biopharmaceutics & drug disposition, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Iguratimod in combination with methotrexate in active rheumatoid arthritis : Therapeutic effects.Zeitschrift fur Rheumatologie · 2016Trial
- Nanofluidic-based electrochemical pump for remotely controlled, on-demand drug delivery.Lab on a chip · 2026Article
- A Semi-Mechanistic Mathematical Model of Immune Tolerance Induction to Support Preclinical Studies of Human Monoclonal Antibodies in Rats.Pharmaceutics · 2025Article
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- Evaluation of analgesic and anti-inflammatory activity of purine-2,6-dione-based TRPA1 antagonists with PDE4/7 inhibitory activity.Pharmacological reports : PR · 2022Article
- Pharmacokinetic/Pharmacodynamic Evaluation of a New Purine-2,6-Dione Derivative in Rodents with Experimental Autoimmune Diseases.Pharmaceutics · 2022Article
- Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.Acta pharmaceutica Sinica. B · 2021Article
- Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution.Pharmaceutics · 2020Article
- Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK/PD Modeling Approach.Pharmaceutical research · 2020Article
- Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis: A Brief Review.Cells · 2019Review
- Methotrexate disposition, anti-folate activity and efficacy in the collagen-induced arthritis mouse model.European journal of pharmacology · 2019Article
- Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.Arthritis research & therapy · 2018Article
- Model-Informed Development and Registration of a Once-Daily Regimen of Extended-Release Tofacitinib.Clinical pharmacology and therapeutics · 2017Article
- CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage.Scientific reports · 2016Article
- Modeling pharmacokinetics/pharmacodynamics of abatacept and disease progression in collagen-induced arthritic rats: a population approach.Journal of pharmacokinetics and pharmacodynamics · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Methotrexate (MTX) is an anchor drug used to treat rheumatoid arthritis (RA), but responsiveness is variable in effectiveness and toxicity. Methotrexate and its polyglutamate conjugates (MTXPG(n)) in red blood cells (RBC) have been associated with patient response. In the current study, 13 collagen-induced arthritic (CIA) rats and 12 healthy rats were given subcutaneous doses of either saline or 0.3 or 1.5 mg/kg per 2 days of MTX from day 21 to 43 post-induction. Blood samples were obtained at various times to measure MTX in plasma, and MTX and MTXPG(n) in RBC. Effects on disease progression were indicated by body weight and paw size. After multiple-doses, RBC MTX reached steady-state (82.4 nm) within 4 days. The MTXPG(2) and MTXPG(3) in RBC kept increasing until the end of the study, attaining 12.5 and 17.7 nm. Significant weight loss was observed after dosing with 1.5 mg/kg/2 days, whereas moderate effectiveness was observed after dosing with 0.3 mg/kg/2 days. A pharmacokinetic/pharmacodynamic/disease (PK/PD/DIS) model with indirect mechanisms and transduction components incorporating plasma MTX, RBC MTX and RBC MTXPG(n) concentrations, and paw size was developed using naïve data pooling and ADAPT 5. The PK/PD in CIA rats dosed at 0.3 mg/kg/2 days were captured well by our proposed model. Methotrexate showed modest (I(maxd) = 0.16) but sensitive (IC(50d) = 0.712 nm) effectiveness on paw edema. The higher dose produced toxicity. The proposed model offers improved understanding of the effects of methotrexate on rheumatoid arthritis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.