ArticlePharmaceutical research2012
Pharmacokinetic/pharmacodynamic modeling of methylprednisolone effects on iNOS mRNA expression and nitric oxide during LPS-induced inflammation in rats.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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
6 citing papers in PubMed, 16 citations in OpenAlex.
- Pharmacokinetic/Pharmacodynamic Modeling of Dexamethasone Anti-Inflammatory and Immunomodulatory Effects in LPS-Challenged Rats: A Model for Cytokine Release Syndrome.The Journal of pharmacology and experimental therapeutics · 2023Article
- Pharmacokinetic-Pharmacodynamic Modeling for Coptisine Challenge of Inflammation in LPS-Stimulated Rats.Scientific reports · 2019Article
- Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti-inflammatory and epigenetic gene expression.Biopharmaceutics & drug disposition · 2018Article
- Semi-Mechanism-Based Pharmacodynamic Model for the Anti-Inflammatory Effect of Baicalein in LPS-Stimulated RAW264.7 Macrophages.Frontiers in pharmacology · 2018Article
- Pharmacokinetics and Pharmacodynamics of the Triterpenoid Ursolic Acid in Regulating the Antioxidant, Anti-inflammatory, and Epigenetic Gene Responses in Rat Leukocytes.Molecular pharmaceutics · 2017Article
- Pharmacokinetic/pharmacodynamic modeling in inflammation.Critical reviews in biomedical engineering · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeIncreased expression of inducible nitric oxide synthase (iNOS) resulting in nitric oxide elevation represents an important component of inflammatory responses. We assess the effects of methylprednisolone (MPL) on these processes during endotoxin-induced acute inflammation and provide a mechanism-based model to quantitatively describe them.
methodsMale Lewis rats were dosed with lipopolysaccharide (50 μg/kg LPS) alone or with methylprednisolone (10 and 50 mg/kg) and sacrificed at different time points. Plasma MPL, lung iNOS mRNA expression, plasma nitric oxide (NO) and other physiological factors were measured. Sodium nitrate (750 μmole/kg) was given to a separate cohort of rats to assess NO disposition kinetics. PK-PD modeling was performed with ADAPT 5.
resultsDisposition kinetics of plasma MPL and NO showed bi-exponential decline and were described by two-compartment models. LPS increased expression of iNOS mRNA in lung and increased plasma NO, while MPL dosing palliated this increase in a dose-dependent manner. These effects were well captured using tandem indirect response and precursor-pool models.
conclusionThe model provides a quantitative assessment of the suppression of NO production by MPL and shows that the major effects are at the transcriptional level by reducing expression of iNOS mRNA.
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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.