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posted by Helmut – Vienna, Austria, 2012-06-12 20:23 (4708 d 23:00 ago) – Posting: # 8716
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Hi John!

❝ What if some subjects do not fit with the same PK model?

Then I would consider the 2-step method nonsense. Average subjects with similar PK only. Imagine you get a long apparent (!) half life in a 1-compartment and a 2-compartment. In the former case this is linked to elimination from the central compartment¹ but in the latter case there are two possibilities

Slow elimination from V_c – like in the one-compartment case; fast exchange between central and peripheral (k₁₂ & k₂₁ >> k₁₀).
Fast elimination from V_c, but a slow distribution phase (either k₁₂ or k₂₁).

Now we end up with parameter identifiability problems.²
In comparing subjects following 1- & 2-compartment PK it would be possible to average the ‘central’ compartment and the elimination – but only in case #1, IMHO.

Nitpicking there is no ‘central’ compartment because we don’t have peripheral(s) in this model. The whole body is seen as a big bucket (yeah: our bones are assumed to be made out of the same stuff as the vitreous body. Funny idea). One-compartment PK doesn’t exist – sometimes the analytical method is not able to catch the slower phase.
Bonate PL. Pharmacokinetic-Pharmacodynami Modeling and Simulation.
‘Identifiability of Compartmental Models’, New York: Springer; 2006. p. 29–37.

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Helmut Schütz

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Complete thread:

which time points to use for calculation of kel Samir Malhotra 2012-06-12 10:59
- which time points to use for calculation of kel ElMaestro 2012-06-12 11:16
  - which time points to use for calculation of kel Samir Malhotra 2012-06-12 11:28
    - which time points to use for calculation of kel ElMaestro 2012-06-12 11:35
    - which time points to use for calculation of kel Samir Malhotra 2012-06-12 11:59
      - which time points to use for calculation of kel ElMaestro 2012-06-12 12:39
        
        Wetware required Helmut 2012-06-12 15:59
        
        Geometric, arithmetic, median ... ? d_labes 2012-06-12 16:28
        
        Geometric, arithmetic, median ... ? Helmut 2012-06-12 17:51
        
        Geometric, arithmetic, median ... ? d_labes 2012-06-13 08:53
        
        Geometric, arithmetic, median ... ? Helmut 2012-06-13 08:58
        
        Wetware required jag009 2012-06-12 17:38
        
        Wetware required Helmut 2012-06-12 19:50
        
        Wetware required jag009 2012-06-12 17:40
        
        Wetware requiredHelmut 2012-06-12 18:23
        
        Wetware required Samir Malhotra 2012-06-13 09:39
        
        Fit individuals; ignore BQLs Helmut 2012-06-13 20:33