ArticlePharmaceutical research2018
The Extended Clearance Concept Following Oral and Intravenous Dosing: Theory and Critical Analyses.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis 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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Intestinal Efflux Transporters P-gp and BCRP Are Not Clinically Relevant in Apixaban Disposition.Pharmaceutical research · 2020Pooled it
- Effect of Rifampin-Mediated OATP1B1 and OATP1B3 Transporter Inhibition on the Pharmacokinetics of the P2Y12 Receptor Antagonist Selatogrel.Clinical and translational science · 2020Trial
- Mathematical Modeling in Drug Metabolism and Pharmacokinetics: Correct In Vitro, Not Always Valid In Vivo.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Net Influx Rather Than Directional Rates: Re-evaluating Transporter Characterization In Vivo and In Vitro for Renal and Hepatic Clearance.The AAPS journal · 2025Review
- Drug Metabolism and Pharmacokinetic Evaluation of a Novel RNase H2 Inhibitor for the Treatment of Triple-Negative Breast Cancer.Pharmaceutics · 2025Article
- Response to the commentary on "are all measures of liver KpEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025Article
- Application of Kirchhoff's Laws to pharmacologic and pharmacokinetic analyses.Pharmacological reviews · 2025Review
- Are all measures of liver KpEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024Article
- EvaluatingFrontiers in pharmacology · 2024Review
- Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model.CPT: pharmacometrics & systems pharmacology · 2024Article
- Physiologically Based Pharmacokinetic Modeling Approaches for Patients With SARS-CoV-2 Infection: A Case Study With Imatinib.Journal of clinical pharmacology · 2022Article
- 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
- 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
- A Simple Methodology to Differentiate Changes in Bioavailability From Changes in Clearance Following Oral Dosing of Metabolized Drugs.Clinical pharmacology and therapeutics · 2020Article
- Challenging the Relevance of Unbound Tissue-to-Blood Partition Coefficient (KpPharmaceutical research · 2020Article
- How Transporters Have Changed Basic Pharmacokinetic Understanding.The AAPS journal · 2019Review
- Understanding drug-drug interaction and pharmacogenomic changes in pharmacokinetics for metabolized drugs.Journal of pharmacokinetics and pharmacodynamics · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo derive the theoretical basis for the extended clearance model of organ elimination following both oral and IV dosing, and critically analyze the approaches previously taken.
methodsWe derived from first principles the theoretical basis for the extended clearance concept of organ elimination following both oral and IV dosing and critically analyzed previous approaches.
resultsWe point out a number of critical characteristics that have either been misinterpreted or not clearly presented in previously published treatments. First, the extended clearance concept is derived based on the well-stirred model. It is not appropriate to use alternative models of hepatic clearance. In analyzing equations, clearance terms are all intrinsic clearances, not total drug clearances. Flow and protein binding parameters should reflect blood measurements, not plasma values. In calculating the AUC
conclusionsThe extended clearance concept is a powerful tool to evaluate drug-drug interactions, pharmacogenomic and disease state variance but evaluating the AUC
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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.