ArticleJournal of pharmacokinetics and pharmacodynamics2014
A "middle-out" approach to human pharmacokinetic predictions for OATP substrates using physiologically-based pharmacokinetic modeling.
Article in Journal of pharmacokinetics and pharmacodynamics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.Drug metabolism and disposition: the biological fate of chemicals · 2016Pooled 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
- Rosuvastatin PBPK Modeling: Incorporating Liver Concentrations and Effects of Ethnicity, Genetic Polymorphisms, Lactone Formation, DDI and Pregnancy.CPT: pharmacometrics & systems pharmacology · 2025Article
- Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Physiologically Based Pharmacokinetic Model of OATP1B Substrates with a Nonlinear Mixed Effect Approach: Estimating Empirical In Vitro-to-In Vivo Scaling Factors.Clinical pharmacokinetics · 2024Article
- Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Integrated Use of In Vitro and In Vivo Information for Comprehensive Prediction of Drug Interactions Due to Inhibition of Multiple CYP Isoenzymes.Clinical pharmacokinetics · 2023Article
- Exploring the Pharmacokinetic Mysteries of the Liver: Application of Series Compartment Models of Hepatic Elimination.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- In Vitro-In Vivo Extrapolation and Scaling Factors for Clearance of Human and Preclinical Species with Liver Microsomes and Hepatocytes.The AAPS journal · 2023Article
- A "middle-out approach" for the prediction of human drug disposition from preclinical data using simplified physiologically based pharmacokinetic (PBPK) models.CPT: pharmacometrics & systems pharmacology · 2023Article
- Article
- In Vitro - in Vivo Extrapolation of Hepatic Clearance in Preclinical Species.Pharmaceutical research · 2022Article
- Advancing Estimation of Hepatobiliary Clearances in Physiologically Based Pharmacokinetic Models of Rosuvastatin Using Human Hepatic Concentrations.Pharmaceutical research · 2021Article
- Navigating Through Cell-Based In vitro Models Available for Prediction of Intestinal Permeability and Metabolism: Are We Ready for 3D?The AAPS journal · 2021Article
- Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making.European journal of drug metabolism and pharmacokinetics · 2021Article
- Lost in modelling and simulation?ADMET & DMPK · 2021Article
- Assessing the impact of cystic fibrosis on the antipyretic response of ibuprofen in children: Physiologically-based modeling as a candle in the dark.British journal of clinical pharmacology · 2020Article
- Physiologically-Based Pharmacokinetic Models for Evaluating Membrane Transporter Mediated Drug-Drug Interactions: Current Capabilities, Case Studies, Future Opportunities, and Recommendations.Clinical pharmacology and therapeutics · 2020Review
- Drug Concentration Asymmetry in Tissues and Plasma for Small Molecule-Related Therapeutic Modalities.Drug metabolism and disposition: the biological fate of chemicals · 2019Review
- Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer.CPT: pharmacometrics & systems pharmacology · 2019Article
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Physiologically based pharmacokinetic (PBPK) models provide a framework useful for generating credible human pharmacokinetic predictions from data available at the earliest, preclinical stages of pharmaceutical research. With this approach, the pharmacokinetic implications of in vitro data are contextualized via scaling according to independent physiological information. However, in many cases these models also require model-based estimation of additional empirical scaling factors (SFs) in order to accurately recapitulate known human pharmacokinetic behavior. While this practice clearly improves data characterization, the introduction of empirically derived SFs may belie the extrapolative power commonly attributed to PBPK. This is particularly true when such SFs are compound dependent and/or when there are issues with regard to identifiability. As such, when empirically-derived SFs are necessary, a critical evaluation of parameter estimation and model structure are prudent. In this study, we applied a global optimization method to support model-based estimation of a single set of empirical SFs from intravenous clinical data on seven OATP substrates within the context of a previously published PBPK model as well as a revised PBPK model. The revised model with experimentally measured unbound fraction in liver, permeability between liver compartments, and permeability limited distribution to selected tissues improved data characterization. We utilized large-sample approximation and resampling approaches to estimate confidence intervals for the revised model in support of forward predictions that reflect the derived uncertainty. This work illustrates an objective approach to estimating empirically-derived SFs, systematically refining PBPK model performance and conveying the associated confidence in subsequent forward predictions.
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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.