ArticleBritish journal of pharmacology2008
Population pharmacokinetic modelling of the enterohepatic recirculation of diclofenac and rofecoxib in rats.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed.
- Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats, Dogs, and Humans.The AAPS journal · 2015Trial
- A quantitative enterohepatic circulation model: development and evaluation with tesofensine and meloxicam.Clinical pharmacokinetics · 2009Trial
- Pharmacokinetics and Efficacy of a Cyanide-Neutralizing [MoJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Article
- Article
- Impact of Species and Tissue Differences on In Vitro Glucuronidation of Diclofenac.Molecules (Basel, Switzerland) · 2024Article
- A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.Molecular pharmaceutics · 2024Article
- Pharmacokinetic Simulation and Area under the Curve Estimation of Drugs Subject to Enterohepatic Circulation.Pharmaceutics · 2024Article
- Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2021Review
- Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat.Pharmaceutical research · 2016Article
- Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.Acta pharmacologica Sinica · 2016Article
- Population pharmacokinetic model for cancer chemoprevention with sulindac in healthy subjects.Journal of clinical pharmacology · 2013Article
- Targeting cyclooxygenase-2 in depression is not a viable therapeutic approach and may even aggravate the pathophysiology underpinning depression.Metabolic brain disease · 2012Review
- Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats.Acta pharmacologica Sinica · 2012Article
- Cattle bile aggravates diclofenac sodium-induced small intestinal injury in mice.Evidence-based complementary and alternative medicine : eCAM · 2011Article
- cPLA2 is protective against COX inhibitor-induced intestinal damage.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeEnterohepatic recirculation (EHC) is a common pharmacokinetic phenomenon that has been poorly modelled in animals. The presence of EHC leads to the appearance of multiple peaks in the concentration-time profile and increased exposure, which may have implications for drug effect and extrapolation across species. The aim of this investigation was to develop a population pharmacokinetic model for diclofenac and rofecoxib that describes EHC and to assess its consequence for the pharmacodynamics of both drugs. EXPERIMENTAL APPROACH: The pharmacokinetics of diclofenac and rofecoxib was characterized in male rats following intravenous, intraperitoneal and oral administration. Blood samples were collected at pre-defined time points after dosing to determine plasma concentrations over time. A parametric approach using nonlinear mixed effects modelling was applied to describe EHC, whilst simulations were used to evaluate its impact on PGE(2) inhibition. KEY
resultsFor diclofenac, EHC was described by a compartmental model with periodic transfer rate and metabolite formation rate. For rofecoxib, EHC modelling required a conversion compartment with first-order recycling rate and lag time. Based on model predictions, EHC causes an increase of 95% in the systemic exposure to diclofenac and of 15% in the exposure to rofecoxib. In addition, EHC prolongs the inhibition of PGE(2) and increases the duration of the anti-inflammatory effect (24 h for rofecoxib 10 mg kg(-1)) without affecting maximum inhibition. CONCLUSIONS AND IMPLICATIONS: Our findings show the relevance of exploring EHC in a quantitative manner to accurately interpret pharmacodynamic findings in vivo, in particular when scaling across species.
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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.