ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Hepatic Clearance Predictions from In Vitro-In Vivo Extrapolation and the Biopharmaceutics Drug Disposition Classification System.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 51 citations in OpenAlex.
- Beyond the Michaelis-Menten: Evaluation of a tQSSA-Based IVIVE Approach for Predicting In Vivo Intrinsic Clearance From Hepatocyte Assays.CPT: pharmacometrics & systems pharmacology · 2026Article
- Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Structure-Based Discovery of Hsp90/HDAC6 Dual Inhibitors Targeting Aggressive Prostate Cancer.Journal of medicinal chemistry · 2025Article
- Prediction of metabolism and solubility of tablet-form drugs according to the biopharmaceutical drug disposition classification system.ADMET & DMPK · 2025Article
- Can In Vitro-In Vivo Extrapolation Be Successful? Recognizing the Incorrect Clearance Assumptions.Clinical pharmacology and therapeutics · 2022Review
- Does Addition of Protein to Hepatocyte or Microsomal In Vitro Incubations Provide a Useful Improvement in In Vitro-In Vivo Extrapolation Predictability?Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- 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
- Recent developments inDrug metabolism reviews · 2021Article
- Successful and Unsuccessful Prediction of Human Hepatic Clearance for Lead Optimization.Journal of medicinal chemistry · 2021Review
- Albumin-Mediated Uptake Improves Human Clearance Prediction for Hepatic Uptake Transporter Substrates Aiding a Mechanistic In Vitro-In Vivo Extrapolation (IVIVE) Strategy in Discovery Research.The AAPS journal · 2020Article
- 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
- In Vitro-In Vivo Inaccuracy: The CYP3A4 Anomaly.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Reconciling Human-Canine Differences in Oral Bioavailability: Looking beyond the Biopharmaceutics Classification System.The AAPS journal · 2019Article
- In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction.Journal of pharmaceutical sciences · 2019Article
- Interlaboratory Variability in Human Hepatocyte Intrinsic Clearance Values and Trends with Physicochemical Properties.Pharmaceutical research · 2019Article
- Relevance of In Vitro Metabolism Models to PET Radiotracer Development: Prediction of In Vivo Clearance in Rats from Microsomal Stability Data.Pharmaceuticals (Basel, Switzerland) · 2019Article
- The Presence of a Transporter-Induced Protein Binding Shift: A New Explanation for Protein-Facilitated Uptake and Improvement for In Vitro-In Vivo Extrapolation.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- The Extended Clearance Concept Following Oral and Intravenous Dosing: Theory and Critical Analyses.Pharmaceutical research · 2018Article
- An examination of protein binding and protein-facilitated uptake relating to in vitro-in vivo extrapolation.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Predicting in vivo pharmacokinetic parameters such as clearance from in vitro data is a crucial part of the drug-development process. There is a commonly cited trend that drugs that are highly protein-bound and are substrates for hepatic uptake transporters often yield the worst predictions. Given this information, 11 different data sets using human microsomes and hepatocytes were evaluated to search for trends in accuracy, extent of protein binding, and drug classification based on the Biopharmaceutics Drug Disposition Classification System (BDDCS), which makes predictions about transporter effects. As previously reported, both in vitro systems (microsomes and hepatocytes) gave a large number of inaccurate results, defined as predictions falling more than 2-fold outside of in vivo values. The weighted average of the percentage of inaccuracy was 66.5%. BDDCS class 2 drugs, which are subject to transporter effects in vivo unlike class 1 compounds, had a higher percentage of inaccurate predictions and often had slightly larger bias. However, since the weighted average of the percentage of inaccuracy was still high in both classes (81.9% for class 2 and 62.3% for class 1), it may be currently hard to use BDDCS class to predict potential accuracy. The results of this study emphasize the need for improved in vitro to in vivo extrapolation experimental methods, as using physiologically based scaling is still not accurate, and BDDCS cannot currently help predict accurate results.
Indexed as
Identifiers
What OpenQuestion holds
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.