Bioequivalence and Bioavailability Forum

Nonparametric superposition [General Statistics]

posted by Helmut – Vienna, Austria, 2013-11-24 15:30 (4178 d 11:54 ago) – Posting: # 11952
Views: 16,026

Hi Chirag,

❝ Is there any way of simulating the data to predict steady state from the pilot study data?

Two ways.

PK modeling.
Nonparametric superposition.

For both you need a reliable estimate of the slowest phase (elimination or absorption if k_a < k_el) and have to assume:

Independence of doses (no auto-induction or -inhibition).
identical rate and extent of absorption, and
identical clearances.

#1 is tricky. Therefore, I would suggest #2.

At the multiples of τ stack the single dose profile on top of remaining concentrations.
Add the estimated time course of the slowest phase of the preceding profiles.
Don’t use mean values. In order to plan for the calibration range of the analytical method in the multiple dose study perform the superposition of the most “extreme” subjects of the pilot study. Allow for some “headroom” on both sides. In the example I would suggest LLOQ ≤20 and ULOQ ≥300.

For an example in WinNonlin 5.x see this post. Easier in Phoenix.

[image]

BTW, look at the steady state profiles and the inserted plot. Compared to single dose t_max slightly shifts towards earlier times. Sometimes it makes sense not to blindly use the single dose’s sampling time schedule, but to adjust it accordingly.

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Helmut Schütz

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Complete thread:

Simulation of data to predict Steady state cakhatri 2013-11-24 10:13 [General Statistics]
- Nonparametric superpositionHelmut 2013-11-24 14:30
  - Nonparametric superposition jag009 2013-11-24 23:13
    - Nonlinear nightmare Helmut 2013-11-25 02:56
      - Nonlinear nightmare jag009 2013-11-25 17:43
        
        Nonlinear nightmare Helmut 2013-11-26 14:32
        
        Nonlinear nightmare jag009 2013-11-26 16:00
        
        OT: Vienna Helmut 2013-11-26 16:27
        
        OT: Vienna jag009 2013-11-26 17:29
        
        OT: Vienna Helmut 2013-11-27 13:04
  - Conc at dosing interval jag009 2013-11-25 17:48
    - Conc at dosing interval Helmut 2013-11-26 15:01
      - Conc at dosing interval jag009 2013-11-26 17:31
        
        Conc at dosing interval Helmut 2013-11-27 13:10
        
        Conc at dosing interval jag009 2013-11-27 20:00
        Passing SD and Failing MD luvblooms 2013-11-28 09:19
        
        Passing SD and Failing MD Helmut 2013-11-29 17:29
        
        Passing SD and Failing MD luvblooms 2013-11-29 18:57
        
        Cτ predictive of Cmin Helmut 2013-11-30 17:25

Nonparametric superposition [General Sta­tis­tics]

Complete thread:

Nonparametric superposition [General Statistics]