Trial reportPharmaceutical research2015
Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach.
Trial report in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
- Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method.The AAPS journal · 2020Trial
- A Drug-Drug Interaction Study to Evaluate the Effect of TAS-303 on CYP3A Activity in the Small Intestine and Liver.Journal of clinical pharmacology · 2020Trial
- Verification of a Physiologically-based Pharmacokinetic Model for Predicting CYP3A4-mediated Simvastatin and Simvastatin Acid Drug-drug Interactions.The AAPS journal · 2026Article
- Evaluating genotype-treatment interactions for high-risk medications in British general practice: a retrospective cohort study using UK Biobank.The British journal of general practice : the journal of the Royal College of General Practitioners · 2026Article
- Population Physiologically-Based Pharmacokinetic Modeling to Determine Ontogeny: A Quantitative Clinical Pharmacology Example in Pediatric Rare Disease.CPT: pharmacometrics & systems pharmacology · 2026Review
- Utilizing Physiologically Based Pharmacokinetic Modeling and Virtual Simulation for Simvastatin Tablets to Evaluate the Sensitivity of Using Parent vs Metabolite as Analyte on Bioequivalence Assessment.The AAPS journal · 2025Article
- Integrated Physiologically-based Pharmacokinetic Model with a Quantitative Systems Pharmacology and Toxicology Model for Statins in Disease Population. Part 2: MIDD and MIPD Applications.The AAPS journal · 2025Article
- Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry.Pharmaceutics · 2024Review
- Physiologically based pharmacokinetics modeling and transporter proteomics to predict systemic and local liver and muscle disposition of statins.CPT: pharmacometrics & systems pharmacology · 2024Article
- Insight into Risk Factors, Pharmacogenetics/Genomics, and Management of Adverse Drug Reactions in Elderly: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Does the choice of applied physiologically-based pharmacokinetics platform matter? A case study on simvastatin disposition and drug-drug interaction.CPT: pharmacometrics & systems pharmacology · 2022Article
- In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models.The AAPS journal · 2022Article
- Physiologically Based Pharmacokinetic Modeling of Transporter-Mediated Hepatic Disposition of Imaging Biomarker Gadoxetate in Rats.Molecular pharmaceutics · 2021Article
- A hybrid modeling approach for assessing mechanistic models of small molecule partitioning in vivo using a machine learning-integrated modeling platform.Scientific reports · 2021Article
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Drug-drug-gene interactions and adverse drug reactions.The pharmacogenomics journal · 2020Review
- Interpretation of Drug Interaction Using Systemic and Local Tissue Exposure Changes.Pharmaceutics · 2020Review
- Mechanistic Models as Framework for Understanding Biomarker Disposition: Prediction of Creatinine-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2020Article
- Challenging the Relevance of Unbound Tissue-to-Blood Partition Coefficient (KpPharmaceutical research · 2020Article
- In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing.Pharmaceutics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeTo develop a population physiologically-based pharmacokinetic (PBPK) model for simvastatin (SV) and its active metabolite, simvastatin acid (SVA), that allows extrapolation and prediction of their concentration profiles in liver (efficacy) and muscle (toxicity).
methodsSV/SVA plasma concentrations (34 healthy volunteers) were simultaneously analysed with NONMEM 7.2. The implemented mechanistic model has a complex compartmental structure allowing inter-conversion between SV and SVA in different tissues. Prior information for model parameters was extracted from different sources to construct appropriate prior distributions that support parameter estimation. The model was employed to provide predictions regarding the effects of a range of clinically important conditions on the SV and SVA disposition.
resultsThe developed model offered a very good description of the available plasma SV/SVA data. It was also able to describe previously observed effects of an OATP1B1 polymorphism (c.521 T > C) and a range of drug-drug interactions (CYP inhibition) on SV/SVA plasma concentrations. The predicted SV/SVA liver and muscle tissue concentrations were in agreement with the clinically observed efficacy and toxicity outcomes of the investigated conditions.
conclusionsA mechanistically sound SV/SVA population model with clinical applications (e.g., assessment of drug-drug interaction and myopathy risk) was developed, illustrating the advantages of an integrated population PBPK approach.
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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.