ArticleJournal of pharmaceutical sciences2019
In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction.
Article in Journal of pharmaceutical sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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.
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Who cites it
23 citing papers in PubMed.
- Prediction of a clinically effective dose of THY1773, a novel VBiopharmaceutics & drug disposition · 2021Trial
- PK-Informed Microphysiological Systems: From Dynamic Dosing to Quantitative In Vitro-In Vivo Translation.Pharmaceutics · 2026Review
- Orbitrap HRMS-Based Comprehensive Metabolite Characterization of Duvelisib in Cross-Species Hepatocytes.Rapid communications in mass spectrometry : RCM · 2026Article
- Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- PKSmart: an open-source computational model to predict intravenous pharmacokinetics of small molecules.Journal of cheminformatics · 2025Article
- Article
- Determination of Intrinsic Clearance and Fraction Unbound in Human Liver Microsomes and In Vitro-In Vivo Extrapolation of Human Hepatic Clearance for Marketed Central Nervous System Drugs.European journal of drug metabolism and pharmacokinetics · 2025Article
- Inhibition of Tacrolimus Metabolism by Cannabidiol and Its Metabolites In Vitro.Clinical and translational science · 2025Article
- Liver-on-chips for drug discovery and development.Materials today. Bio · 2024Review
- A Combination of Machine Learning and PBPK Modeling Approach for Pharmacokinetics Prediction of Small Molecules in Humans.Pharmaceutical research · 2024Review
- Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin.Metabolites · 2022Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Unravelling the pharmacokinetics of aflatoxin B1:Frontiers in microbiology · 2022Article
- Article
- The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood StagePharmaceutics · 2021Article
- Prediction of hepatic drug clearance with a human microfluidic four-cell liver acinus microphysiology system.Toxicology · 2021Article
- There is Only One Valid Definition of Clearance: Critical Examination of Clearance Concepts Reveals the Potential for Errors in Clinical Drug Dosing Decisions.The AAPS journal · 2021Article
- Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization.Journal of medicinal chemistry · 2021Review
- Prediction of Drug Clearance from Enzyme and Transporter Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Investigating the Theoretical Basis for In Vitro-In Vivo Extrapolation (IVIVE) in Predicting Drug Metabolic Clearance and Proposing Future Experimental Pathways.The AAPS journal · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.
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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.