Bioequivalence and Bioavailability Forum • WinNonlin/Phoenix extrapolation to t=tau

WinNonlin/Phoenix extrapolation to t=tau [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2010-02-03 21:26 (5975 d 16:33 ago) – Posting: # 4705
Views: 27,691

Dear Ray!

❝ "Actual time of sampling should be used in the estimation of the pharmacokinetic parameters […] In multiple-dose studies, the pre-dose sample should be taken immediately before (within 5 minutes) dosing." Now, while inserting time in winnonlin for 2nd, 3rd… predose concentration, whether we have to insert the actual time point/ the protocol specified time? For example if dosing interval is 24 hours, in that case wheather to use 23.92/ 24.00 for calculation of pharmacokinetic parameters?

Which version of WinNonlin? Can you come up with a numerical example?
Are you talking about something like this?


 0     0    0     0    0     0

23.92  1   24.00  1   24.08  1

36.00  2   36.00  2   36.00  2

48.00  1   48.00  1   48.00  1

A dosing interval of 24 will give an AUC_τ of 36 (linear trapezoidal rule) for the first and second data set, and 35.96 for the third. WinNonlin 5.2.1 will interpolate to t=24 (the τ you have specified). In the text output the time point 24.00 will be marked (@) and the line
@) Note - the concentration at dose time was added for extrapolation purposes.
will clarify the method.
You get the same results in Phoenix 6.1; The note about extrapolation to t=τ is given in the core-output.
I don’t see a problem here - or what would you suggest?
Phoenix is more flexible in setting up individual dosings. You may even give delayed administrations and define partial areas based on actual time points, etc. But do we really need that?

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Complete thread:

EMA BE guideline - final version Ohlbe 2010-01-28 18:31 [Regulatives / Guidelines]
- Final version published Helmut 2010-01-29 14:29
  - Final version published ElMaestro 2010-01-29 17:02
    - Statistix Helmut 2010-01-29 17:30
      - Statistix ElMaestro 2010-01-29 18:11
    - Calories ;-) Helmut 2010-01-29 19:22
      - Calories ;-) ElMaestro 2010-01-29 20:43
        
        Calories ;-) Helmut 2010-01-29 21:08
      - Variable calories d_labes 2010-02-01 12:05
    - ANOVA only - no doubts Helmut 2010-02-10 23:41
      - ANOVA only - no doubts ElMaestro 2010-02-12 21:09
  - Final EMA oracle d_labes 2010-02-01 11:53
    - Final EMA oracle Helmut 2010-02-01 12:28
    - Final EMA oracle ElMaestro 2010-02-01 12:50
      - More then two EMA oracles d_labes 2010-02-01 13:30
        
        Less of an issue ElMaestro 2010-02-01 15:29
        
        Less or More of an issue d_labes 2010-02-01 16:53
        
        Less or More of an issue ElMaestro 2010-02-01 17:22
        
        Effective with 1 Aug 2010 Helmut 2010-02-02 00:55
        Bias? ElMaestro 2010-02-04 11:27
        
        Bias? Helmut 2010-02-05 02:03
        
        Bias? ElMaestro 2010-02-05 09:33
        
        Bias? Helmut 2010-02-05 10:21
        
        Bias? d_labes 2010-02-05 13:59
        Bias? ElMaestro 2010-02-05 16:00
        
        Bias? Helmut 2010-02-05 19:14
      - Final EMA oracle Helmut 2010-02-01 13:43
        
        Final EMA oracle ElMaestro 2010-02-01 14:54
        
        Final EMA oracle d_labes 2010-02-01 15:20
        
        Teaching Helmut 2010-02-01 16:07
  - Cmin really gone? tmax reappeared? d_labes 2010-02-01 14:02
    - Cmin really gone. tmax reappeared - but how? Helmut 2010-02-01 23:30
  - Interpol or not d_labes 2010-02-01 14:52
    - Interpol! Helmut 2010-02-02 00:02
      - Interpol! ray_be 2010-02-03 18:31
        
        WinNonlin/Phoenix extrapolation to t=tauHelmut 2010-02-03 20:26
  - Meta-analysis Helmut 2010-02-07 17:41
  - Final version published Panks.79 2010-03-08 07:22
    - Cmin for MR-formulations? Helmut 2010-03-08 18:16
      - Cmin for MR-formulations? Marcel 2010-04-23 10:09
        
        MR-Guideline? Helmut 2010-04-23 12:34
- Overview of comments published Helmut 2010-02-10 18:33
  - Comments commented d_labes 2010-02-11 08:19
  - Definition of Cmin by EMEA Ravi 2010-03-13 12:05
    - The EMA’s Cmin & WinNonlin Helmut 2010-03-13 12:52