ArticleActa pharmacologica Sinica2012
Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats.
Article in Acta pharmacologica Sinica, 2012. 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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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Impact of Individual and Cassette Administration on Pharmacokinetics of Prednisolone, Diclofenac, and Methotrexate in a Rodent Model of Rheumatoid Arthritis.Recent advances in inflammation & allergy drug discovery · 2026Article
- Phytochemical Composition and Antioxidant Activity of Manuka Honey and Ohia Lehua Honey.Nutrients · 2025Article
- Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments.International journal of molecular sciences · 2020Article
- Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.Acta pharmacologica Sinica · 2016Article
- Evaluation of a Postoperative Pain-Like State on Motivated Behavior in Rats: Effects of Plantar Incision on Progressive-Ratio Food-Maintained Responding.Drug development research · 2015Article
- Comparative bioavailability and tolerability of single and multiple doses of 2 diclofenac sodium sustained-release tablet formulations in fasting, healthy chinese male volunteers.Current therapeutic research, clinical and experimental · 2013Article
- Pharmacometrics: a quantitative tool of pharmacological research.Acta pharmacologica Sinica · 2012Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E(2) (PGE(2)) as a biomarker.
methodsThe pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE(2) level in the rats was measured using an enzyme immunoassay. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE(2) production. The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE(2) production in blood cells was investigated in vitro.
resultsSimilar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats. Diclofenac significantly decreased the plasma levels of PGE(2) in both normal and arthritic rats. The inhibitory effect on PGE(2) levels in the plasma was in proportion to the plasma concentration of diclofenac. No delay in the onset of inhibition was observed, suggesting that the effect compartment was located in the central compartment. An inhibitory effect sigmoid I(max) model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE(2) production in vivo. The I(max) model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE(2) production in blood cells in vitro.
conclusionArthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats, but the pharmacodynamics of diclofenac is slightly affected. A PK-PD model characterizing an inhibitory effect sigmoid I(max) can be used to fit the relationship between the plasma PGE(2) and diclofenac levels in both normal rats and FCA-induced arthritic rats.
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