ArticleBritish journal of pharmacology2014
Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A Systematic Review of Published Models, Applications, and Model Verification.Drug metabolism and disposition: the biological fate of chemicals · 2015Pooled it
- Transforming Treatment: The Impact of Bariatric Surgery on Oral Drug Absorption.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Predicting drug-drug interactions and optimal dosing of betrixaban with physiologically based pharmacokinetic modeling in patients with renal impairment who were coadministered with P-glycoprotein inhibitors.The Journal of international medical research · 2025Article
- Assessing the relative contribution of CYP3A-and P-gp-mediated pathways to the overall disposition and drug-drug interaction of dabigatran etexilate using a comprehensive mechanistic physiological-based pharmacokinetic model.Frontiers in pharmacology · 2024Article
- Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults.CJC open · 2022Article
- Risk of Hospitalization With Hemorrhage Among Older Adults Taking Clarithromycin vs Azithromycin and Direct Oral Anticoagulants.JAMA internal medicine · 2020Article
- Predicted effect of ticagrelor on the pharmacokinetics of dabigatran etexilate using physiologically based pharmacokinetic modeling.Scientific reports · 2020Article
- A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Model of Dabigatran Etexilate, Dabigatran and Dabigatran Glucuronide in Healthy Adults and Renally Impaired Patients.Clinical pharmacokinetics · 2019Article
- Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors.Journal of geriatric cardiology : JGC · 2019Article
- Warfarin vs. apixaban in nonvalvular atrial fibrillation, and analysis by concomitant antiarrhythmic medication use: A national retrospective study.Research and practice in thrombosis and haemostasis · 2019Article
- Drug interactions between direct-acting oral anticoagulants and calcineurin inhibitors during solid organ transplantation: considerations for therapy.Expert review of clinical pharmacology · 2019Review
- Assessing Potential Drug-Drug Interactions Between Dabigatran Etexilate and a P-Glycoprotein Inhibitor in Renal Impairment Populations Using Physiologically Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2019Article
- Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation.Advances in therapy · 2017Review
- A Physiologically Based Pharmacokinetic Model of Amiodarone and its Metabolite Desethylamiodarone in Rats: Pooled Analysis of Published Data.European journal of drug metabolism and pharmacokinetics · 2016Article
- Cardiovascular pharmacogenomics: current status and future directions.Journal of human genetics · 2016Review
- Physiologically based pharmacokinetic modeling of impaired carboxylesterase-1 activity: effects on oseltamivir disposition.Clinical pharmacokinetics · 2014Article
- The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts.PloS one · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIn vitro inhibitory potency (Ki )-based predictions of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) are hampered by the substantial variability in inhibitory potency. In this study, in vivo-based [I]/Ki values were used to predict the DDI risks of a P-gp substrate dabigatran etexilate (DABE) using physiologically based pharmacokinetic (PBPK) modelling. EXPERIMENTAL APPROACH: A baseline PBPK model was established with digoxin, a known P-gp substrate. The Km (P-gp transport) of digoxin in the baseline PBPK model was adjusted to Km (i) to fit the change of digoxin pharmacokinetics in the presence of a P-gp inhibitor. Then 'in vivo' [I]/Ki of this P-gp inhibitor was calculated using Km (i) /Km . Baseline PBPK model was developed for DABE, and the 'in vivo' [I]/Ki was incorporated into this model to simulate the static effect of P-gp inhibitor on DABE pharmacokinetics. This approach was verified by comparing the observed and the simulated DABE pharmacokinetics in the presence of five different P-gp inhibitors. KEY
resultsThis approach accurately predicted the effects of five P-gp inhibitors on DABE pharmacokinetics (98-133% and 89-104% for the ratios of AUC and Cmax respectively). The effects of 16 other P-gp inhibitors on the pharmacokinetics of DABE were also confidently simulated. CONCLUSIONS AND IMPLICATIONS: 'In vivo' [I]/Ki and PBPK modelling, used in combination, can accurately predict P-gp-mediated DDIs. The described framework provides a mechanistic basis for the proper design of clinical DDI studies, as well as avoiding unnecessary clinical DDI studies.
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