ArticleThe Journal of pharmacology and experimental therapeutics2008
Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pharmacodynamic model for dexamethasone effects in Lewis rats with collagen-induced arthritis.
Article in The Journal of pharmacology and experimental therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Lycopene attenuates dexamethasone induced depression like behavior and immunological dysfunction via restoration of neuro-immune-metabolic homeostasis in rats.Scientific reports · 2026Article
- Triamcinolone-loaded nanocarriers: a novel strategy to mitigate cognitive and emotional sequelae induced by traumatic brain injury via modulation of oxidative stress.Frontiers in behavioral neuroscience · 2025Article
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- The relationship between gender and pharmacology.Current research in pharmacology and drug discovery · 2024Article
- Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?Pharmaceuticals (Basel, Switzerland) · 2023Review
- Development of PBPK model for intra-articular injection in human: methotrexate solution and rheumatoid arthritis case study.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.Pharmacological reviews · 2020Review
- Translational Quantitative Systems Pharmacology in Drug Development: from Current Landscape to Good Practices.The AAPS journal · 2019Review
- Effect of prednisone treatment for 30 and 90 days on bone metabolism in collagen-induced arthritis (CIA) rats.Journal of bone and mineral metabolism · 2018Article
- Modeling Sex Differences in Anti-inflammatory Effects of Dexamethasone in Arthritic Rats.Pharmaceutical research · 2018Article
- Mechanism-Based Disease Progression Model Describing Host-Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia.CPT: pharmacometrics & systems pharmacology · 2018Article
- Modeling Combined Immunosuppressive and Anti-inflammatory Effects of Dexamethasone and Naproxen in Rats Predicts the Steroid-Sparing Potential of Naproxen.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Model-Informed Development and Registration of a Once-Daily Regimen of Extended-Release Tofacitinib.Clinical pharmacology and therapeutics · 2017Article
- A quantitative mechanistic PK/PD model directly connects Btk target engagement andChemical science · 2017Article
- Mathematical modeling of the circadian dynamics of the neuroendocrine-immune network in experimentally induced arthritis.American journal of physiology. Endocrinology and metabolism · 2016Article
- Modeling effects of dexamethasone on disease progression of bone mineral density in collagen-induced arthritic rats.Pharmacology research & perspectives · 2015Article
- Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats.Acta biomaterialia · 2015Article
- Review
- Localized delivery of dexamethasone-21-phosphate via microdialysis implants in rat induces M(GC) macrophage polarization and alters CCL2 concentrations.Acta biomaterialia · 2015Article
- 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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.
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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.