Bioequivalence and Bioavailability Forum • Calculation of time above MIC

Calculation of time above MIC [🇷 for BE/BA]

posted by Helmut – Vienna, Austria, 2008-06-26 20:58 (6140 d 15:58 ago) – Posting: # 1975
Views: 35,704

Dear Aceto81!

❝ ...I'm struggling with the time above the MIC90 and %time above MIC90.

❝ Prats et al. came up with a time of 102.5 hours and 94.9% of total time in SS.

Looking at you data, this seems to be a reasonable value.

❝ I have no idea about how to find the 102.5 hours.

❝ I searched in the forum's archive, in the manual of WinNonLin, on the web, but couldn't find any references.

It's not implemented in WinNonlin; but I'm right now at a conference in London where one of the lecturers is Jason Chittenden of Pharsight - I will ask him.

I don't know any reference either - except one by Jerome Skelly of the FDA, maybe 20 years ago. Start searching with the term "occupany time" or just "occupancy".

❝ Maybe someone can give me some help?

❝ I'm routinely use R, but now I'm also using WinNonLin.

If the values fall below the MIC and come up again (like in your case) do a linear interpolation. An algorithm is like this:

Run a loop through the sampling time points
If two subsequent concentrations include the MIC and the second one is above, tag an "up" marker
If two subsequent concentrations include the MIC and the second one is below, tag a "down" marker
If two subsequent concentrations are >MIC add the time interval to a stack
If two subsequent concentrations are <MIC goto next concentration
For the "up" markers perform a linear interpolation to find out where the "line" intersects the MIC; subtract this time value from the next time point and add it to the stack
For the "down" markers perform a linear interpolation to find out where the "line" intersects the MIC; add this time value to the last time point and add it to the stack
Occupancy time = the value of the stack

I would use rather R than WinNonlin for that purpose, although it shouldn't be that difficult to set it up too.

I just made a unchecked hotel-room quickshot in R; 116.5 hr >0.517 ug/ml within 0 - 124 hr?!!

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Complete thread:

Calculation of time above MIC Aceto81 2008-06-26 16:31 [🇷 for BE/BA]
- Calculation of time above MICHelmut 2008-06-26 18:58
  - Calculation of time above MIC Aceto81 2008-06-26 21:50
    - Calculation of time above MIC Helmut 2008-06-27 00:18
    - Calculation of time above MIC Helmut 2008-06-29 02:24
      - Calculation of time above MIC Aceto81 2008-06-30 15:50
        
        Therapeutic Occupancy Time / MEC Helmut 2008-06-30 16:45
  - Time above MIC (WinNonlin 5.2.1) Helmut 2008-08-08 20:38
    - Time above MIC (WinNonlin 5.2.1) Aceto81 2008-08-12 09:56
      - Time above MIC (WinNonlin 5.2.1) Helmut 2008-08-12 12:32
        
        Time above MIC (R function) Aceto81 2008-08-13 11:19
        
        Time above MIC (R function) Helmut 2008-08-13 13:18
        
        Time above MIC (R function) Aceto81 2008-08-13 15:35
        
        Phoenix-WinNonlin 6.0 released 29 May 2009 SDavis 2009-06-04 10:55
        
        Phoenix-WinNonlin 6.0 Helmut 2009-06-04 11:57
        
        Phoenix-WinNonlin 6.0 - introductory webinars SDavis 2009-06-04 18:50
        
        Phoenix-WinNonlin 6.0 - introductory webinars Helmut 2009-06-04 23:40
    - TimeLow Astea 2017-10-28 22:15
      - PHX/WNL 8.0 vs. previous releases Helmut 2017-10-28 23:20
        
        PHX/WNL 8.0 vs. previous releases Astea 2017-10-28 23:49
      - Occupancy, Half Value Duration, Plateau Time in Phoenix/WinNonlin 8 Helmut 2017-10-30 13:18
        
        Occupancy, Half Value Duration, Plateau Time in Phoenix/WinNonlin 8 Astea 2017-10-31 01:12
        
        Intersections Helmut 2017-10-31 12:32
        
        nobody needs it... Astea 2017-10-31 18:24