Bioequivalence and Bioavailability Forum • Visual inspection of fits (estimation of λ-z)

Visual inspection of fits (estimation of λ-z) [NCA / SHAM]

posted by Helmut – Vienna, Austria, 2025-11-15 13:36 (213 d 08:03 ago) – Posting: # 24500
Views: 2,299

Dear all,

following the posts in this thread some remarks about automatic algorithms in general. See also there.

The selection of the most suitable time interval cannot be left to a programmed algorithm based on mathematical criteria, but necessitates scientific judgment by both the clinical pharmacokineticist and the person who determined the concentrations and knows about their reliability.¹
It should be emphasised that the TTT method has been introduced in this paper to provide a reasonable tool to support visual curve inspection for reliably identifying the mono-exponential terminal phase. Moreover, the TTT method should not be utilised without visual inspection of the respective concentration-time course. Thus, before using this new approach the monophasic shape post the peak of the curve has to be checked visually by means of a semilogarithmic diagram.²
Data must […] always be inspected in order to allow for manual modification of the time interval over which the regression should be made.³
It was shown in simulations of two-compartment models that manual selection by a pharmacokineticist outperforms standard automatic methods.⁴ Our brain is an excellent pattern recognition machine.
Using this methodology, Phoenix will almost always compute an estimate for Lambda Z. It is the user’s responsibility to evaluate the appropriateness of the estimated value.⁵

Hauschke D, Steinijans VW, Pigeot I. Bioequivalence Studies in Drug Development: Methods and Applications. New York: Wiley; 2007. p. 20-3.
Scheerans C, Derendorf H, Kloft C. Proposal for a Standardised Identification of the Mono-Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos. 2008; 29(3): 145–57. doi:10.1002/bdd.596.
Källén A. Computational Pharmacokinetics. Boca Raton: Chapman & Hall/CRC; 2008. p. 43
Noe DA. Performance characteristics of the adjusted r² algorithm for determining the start of the terminal disposition phase and comparison with a simple r² algorithm and a visual inspection method. Pharm Stat. 2019; 1–13. doi:10.1002/pst.1979.
Certara USA, Inc. Princeton, NJ. 7/9/20. Lambda Z or Slope Estimation settings. Online.

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Helmut Schütz

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Science Quotes

Visual inspection of fits (estimation of λ-z)Helmut 2025-11-15 12:36 [NCA / SHAM]
- Visual inspection of fits (estimation of λ-z) ElMaestro 2025-11-15 19:10
  - Wetware 🧠 vs. software 🤖 Helmut 2025-11-16 09:21
  - Manual integrations Ohlbe 2025-11-17 08:32
    - Manual int ElMaestro 2025-11-17 09:35