ArticlePharmaceutical research2011
Pharmacokinetic-pharmacodynamic modeling of the inhibitory effects of naproxen on the time-courses of inflammatory pain, fever, and the ex vivo synthesis of TXB2 and PGE2 in rats.
Article in Pharmaceutical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Modeling Sex Differences in Pharmacokinetics, Pharmacodynamics, and Disease Progression Effects of Naproxen in Rats with Collagen-Induced Arthritis.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- The search for novel analgesics: targets and mechanisms.F1000prime reports · 2015Review
- Differential effects of opioid-related ligands and NSAIDs in nonhuman primate models of acute and inflammatory pain.Psychopharmacology · 2014Article
- Translational PK-PD modeling in pain.Journal of pharmacokinetics and pharmacodynamics · 2013Review
- In vivo and ex vivo inhibition of spinal nerve ligation-induced ectopic activity by sodium channel blockers correlate to in vitro inhibition of NaV1.7 and clinical efficacy: a pharmacokinetic-pharmacodynamic translational approach.Pharmaceutical research · 2013Article
- Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats.Acta pharmacologica Sinica · 2012Article
- Pharmacokinetic/pharmacodynamic modeling in inflammation.Critical reviews in biomedical engineering · 2012Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo quantify and compare the time-course and potency of the analgesic and antipyretic effects of naproxen in conjunction with the inhibition of PGE(2) and TXB(2).
methodsAnalgesia was investigated in a rat model with carrageenan-induced arthritis using a gait analysis method. Antipyretics were studied in a yeast-induced fever model using telemetrically recorded body temperature. Inhibition of TXB(2) and PGE(2) synthesis was determined ex vivo. Pharmacokinetic profiles were obtained in satellite animals. Population PKPD modeling was used to analyze the data.
resultsThe IC(50) values (95% CI) of naproxen for analgesia (27 (0-130) μM), antipyretics (40 (30-65) μM) and inhibition of PGE(2) (13 (6-45) μM) were in similar range, whereas inhibition of TXB(2) (5 (4-8) μM) was observed at lower concentrations. Variability in the behavioral measurement of analgesia was larger than for the other endpoints. The inhibition of fever by naproxen was followed by an increased rebound body temperature.
conclusionDue to better sensitivity and similar drug-induced inhibition, the biomarker PGE(2) and the antipyretic effect would be suitable alternative endpoints to the analgesic effects for characterization and comparisons of potency and time-courses of drug candidates affecting the COX-2 pathway and to support human dose projections.
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