ArticleThe AAPS journal2021
There is Only One Valid Definition of Clearance: Critical Examination of Clearance Concepts Reveals the Potential for Errors in Clinical Drug Dosing Decisions.
Article in The AAPS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Simplifying Pharmacokinetics, Applying it to Drug and Dosage Form Development, and Making Drug Dosage Decisions in Clinical Medicine: The Adaptation of Kirchhoff's Laws from Physics.The AAPS journal · 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
- Commentary: Pharmacokinetic Theory Must Consider Published Experimental Data.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Are all measures of liver KpEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024Article
- An Explanation of Why Dose-Corrected Area Under the Curve for Alternate Administration Routes Can Be Greater than for Intravenous Dosing.The AAPS journal · 2024Article
- Use of Clearance Concepts to Simulate Impact of Interleukin-6 on Drug Elimination Governed by Cytochromes P450 3A4 and Glomerular Filtration Rate.European journal of drug metabolism and pharmacokinetics · 2023Article
- The Uses and Advantages of Kirchhoff's Laws vs. Differential Equations in Pharmacology, Pharmacokinetics, and (Even) Chemistry.The AAPS journal · 2023Article
- Process and System Clearances in Pharmacokinetic Models: Our Basic Clearance Concepts Are Correct.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Review of the application of Kirchhoff's Laws of series and parallel flows to pharmacology: Defining organ clearance.Pharmacology & therapeutics · 2022Review
- Can In Vitro-In Vivo Extrapolation Be Successful? Recognizing the Incorrect Clearance Assumptions.Clinical pharmacology and therapeutics · 2022Review
- Assessment of the Kochak-Benet Equation for Hepatic Clearance for the Parallel-Tube Model: Relevance of Classic Clearance Concepts in PK and PBPK.The AAPS journal · 2021Article
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4 authors.
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Abstract
Drug dosing decisions in clinical medicine and in introducing a drug to market for the past 60 years are based on the pharmacokinetic/clinical pharmacology concept of clearance. We used chemical reaction engineering models to demonstrate the limitations of presently employed clearance measurements based upon systemic blood concentration in reflecting organ clearance. The belief for the last 49 years that in vivo clearance is independent of the mechanistic model for organ clearance is incorrect. There is only one valid definition of clearance. Defining organ clearance solely on the basis of systemic blood concentrations can lead to drug dosing errors when drug effect sites reside either in an eliminating organ exhibiting incremental clearance or in a non-eliminating organ where intraorgan concentration is governed by transporter actions. Attempts to predict clearance are presently hampered by the lack of recognition that what we are trying to predict is a well-stirred model clearance.
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