The AAPS Journal

, 20:36 | Cite as

New Perspectives in Clinical Pharmacokinetics-1: the Importance of Updating the Teaching in Pharmacokinetics that both Clearance and Elimination Rate Constant Approaches Are Mathematically Proven Equally Valid

  • Roger JelliffeEmail author
  • David Bayard
Tutorial AlternativePerspectives for Evaluating Drug Exposure Characteristics in a Population:Avoiding Analysis Pitfalls and Pigeon Holes
Part of the following topical collections:
  1. Theme: Alternative Perspectives for Evaluating Drug Exposure Characteristics in a Population – Avoiding Analysis Pitfalls and Pigeon Holes


The healing professions have only about four main therapeutic tools at their disposal—surgery, drugs, physical therapy, and psychotherapy. For the general profession of internal medicine, drug therapy is its primary tool. Providing an understanding of the state-of-the-art in therapeutic methods, grounded in solid scientific and mathematical rigor, is therefore of the utmost clinical importance for both physicians and clinical pharmacists. This is particularly true where rapidly evolving scientific changes require an up-to-date education upon which students can rely. Unfortunately, relatively little attention has been paid to training clinical pharmacokineticists and physicians to manage drug therapy optimally for patients under their care in their everyday practice. In this paper, we discuss one of these basic deficiencies from the perspective of the longstanding controversy in pharmacokinetic modeling: whether the volume and clearance approach or the volume and rate constant approach is somehow “better”. We examine this controversy using the mathematical principle of invariance, which to our knowledge has not been done before. The conclusion of this analysis is that both approaches are rigorously proven mathematically to be equally valid. We also discuss some implications of these equally valid approaches from the framework of mechanistic and non-compartmental models. Ultimately, the conclusion is that the choice of one parameterization over the other is based on preference or usefulness for research or clinical practice, but no longer, because of this analysis, on science.


clearance model parameterization pharmacokinetics rate constant 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest to disclose.


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.USC Laboratory of Applied Pharmacokinetics and BioinformaticsUniversity of Southern California School of Medicine, Children’s Hospital of Los AngelesLos AngelesUSA

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