ReviewBritish journal of clinical pharmacology2015
Combining the 'bottom up' and 'top down' approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data.
Review in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
130 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Toward a robust tool for pharmacokinetic-based personalization of treatment with tacrolimus in solid organ transplantation: A model-based meta-analysis approach.British journal of clinical pharmacology · 2019Pooled it
- 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
- Simultaneous Ivabradine Parent-Metabolite PBPK/PD Modelling Using a Bayesian Estimation Method.The AAPS journal · 2020Trial
- Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach.Pharmaceutical research · 2015Trial
- Development and Evaluation of Physiologically Based Pharmacokinetic (PBPK) Models to Investigate the Effect of CYP2D6 Polymorphism on Metoclopramide Systemic Exposure.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Age-Driven Physiologically Based Pharmacokinetic Modeling of Empagliflozin: Toward Precision Dosing in Youth.ACS pharmacology & translational science · 2026Article
- Re-Thinking Pharmacokinetics in Ovarian Cancer: What Do Organoids Add?International journal of molecular sciences · 2026Review
- Integration of Machine Learning With PBPK and QSAR Modeling Approaches to Facilitate Drug Discovery and Development.CPT: pharmacometrics & systems pharmacology · 2026Review
- Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Review on Predictive Models and Integration Strategies for Holistic Impact Assessment of Chemicals and Materials.Environmental science & technology · 2026Review
- Integrating Population Approaches With Physiologically Based Pharmacokinetic Models: A Novel Framework for Parameter Estimation.CPT: pharmacometrics & systems pharmacology · 2026Article
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- A clinical drug-drug interaction assessment using physiologically based pharmacokinetic modeling: a case study with chloroquine and colchicine.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio.Pharmaceutical research · 2025Article
- Solubility-Limited Absorption Identified by a Simplified PBPK Model for the Prediction of Positive Food Effect for BCS II/IV Drugs.Clinical pharmacokinetics · 2025Article
- A preliminary exploration of liver microsomes and PBPK to uncover the impact of CYP3A4/5 and CYP2C19 on tacrolimus and voriconazole drug-drug interactions.Scientific reports · 2025Article
- Physiologically Based Pharmacokinetic Model of Cefotaxime in Patients with Impaired Renal Function.Clinical pharmacokinetics · 2025Article
- Computational approaches to predict the toxicity of bioactive natural products: a mini review of methodologies.Food science and biotechnology · 2025Review
- Application of Physiologically-Based Pharmacokinetic (PBPK) Model in Drug Development and in Dietary Phytochemicals.Current pharmacology reports · 2025Review
- Dose Individualisation of Antimicrobials from a Pharmacometric Standpoint: The Current Landscape.Drugs · 2024Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate outside the studied population and experimental conditions. The trade-off for this advantage is a complex system of differential equations with a considerable number of model parameters. When these parameters cannot be informed from in vitro or in silico experiments they are usually optimized with respect to observed clinical data. Parameter estimation in complex models is a challenging task associated with many methodological issues which are discussed here with specific recommendations. Concepts such as structural and practical identifiability are described with regards to PBPK modelling and the value of experimental design and sensitivity analyses is sketched out. Parameter estimation approaches are discussed, while we also highlight the importance of not neglecting the covariance structure between model parameters and the uncertainty and population variability that is associated with them. Finally the possibility of using model order reduction techniques and minimal semi-mechanistic models that retain the physiological-mechanistic nature only in the parts of the model which are relevant to the desired modelling purpose is emphasized. Careful attention to all the above issues allows us to integrate successfully information from in vitro or in silico experiments together with information deriving from observed clinical data and develop mechanistically sound models with clinical relevance.
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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.